The United States is doing so little of the genetic sequencing needed to detect new variants of the coronavirus — like the ones first identified in Great Britain and South Africa — that such mutations are probably proliferating quickly, undetected, experts said.
Now is when genetic sequencing — a process that maps out the genetic code of the particular virus that infected someone so it can be compared with others — would do the most good, while such variants are less prevalent in the U.S. population and action can be taken against them.
“We are in a race against time because of these mutations. And in that race, we are falling behind,” said Mara G. Aspinall, a biomedical diagnostics professor at Arizona State University.
The problem echoes the country’s catastrophic stumbles early in the pandemic, when a lack of testing allowed the virus to spread widely. Currently, only a tiny fraction of all positive coronavirus tests in the United States are forwarded for further sequencing.
Genetic sequencing is important because the coronavirus, like all viruses, mutates as it moves through people. Many changes are inconsequential and do not alter the transmissibility or severity of illness. But if scientists don’t know what strains are moving through the population, the mutations that matter may pop up undetected.
For months, scientists have been sounding alarms and trying to ramp up genetic sequencing of test samples, but the effort has been plagued by a lack of funding, political will and federal coordination, health experts and state officials said.
More equipment, staffing and funding are needed to increase sequencing, experts said, and the federal government has yet to create the infrastructure and procedures needed to receive, process and share that data on a national scale. Centers for Disease Control and Prevention Director Rochelle Walensky said Friday that the government is increasing the level of sequencing nationwide.
“We have scaled up surveillance dramatically just in the last 10 days, in fact. But our plans for scaling up surveillance are even more than what we’ve done so far,” Walensky said.
Ultimately, the country needs real-time data — similar to the dashboards now used to track daily cases, hospitalizations and deaths — to track variants and their prevalence across the country. While sequencing alone won’t stop the spread of more dangerous variants, it gives the country warning and a chance to act as they become more prevalent.
“None of that exists right now. We’re incredibly behind compared to other countries,” said Janet Hamilton, executive director of the Council of State and Territorial Epidemiologists. “We have no idea what is out there in our country. We don’t even know what we don’t know.”
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38th in the world
The U.S. effort is so underdeveloped that it’s impossible to say exactly how many virus cases are sequenced daily.
On Jan. 5, a CDC official told The Washington Post that the United States was averaging roughly 3,000 sequenced coronavirus genomes a week. This week, CDC officials said the country is now averaging roughly 7,000 a week.
The CDC has warned that the variant found in the United Kingdom — which British scientists said could be up to 70 percent more transmissible — could become dominant in the United States by March. Walensky said the CDC can only tell if that projection is accurate by reaching higher rates of sequencing.
The agency has contracted universities to scale up their sequencing to “thousands per week,” Walensky said. It also recently contracted with four private companies — Quest, Labcorp, Illumina and Helix — to conduct more sequencing. By mid-February, those contracts should hit full capacity, analyzing 6,000 samples per week, CDC officials said.
But those numbers remain a fraction of what experts said is needed to accurately track the variants spreading in America.
Illumina estimates that the country needs to sequence 5 percent of its coronavirus cases to detect a new variant when the variant represents about 0.1 percent to 1.0 percent of the country’s cases. Actions to slow such a spread are most effective during these early phases of circulation.
However, the United States so far has only sequenced about 0.32 percent of its total cases, according to a Washington Post analysis. As of late January, the country ranks 38th out of 130 countries reporting whole-genome sequencing data.
The Post created that analysis by combining data from the GISAID Initiative, an independent platform where researchers share viral genome sequences, and the U.K.’s sequencing consortium, as well as case counts from Johns Hopkins University and The Post’s database.
The United States has sequenced 84,177 samples out of 25.7 million cases as of Friday, according to a Washington Post analysis. By comparison, the United Kingdom, in ninth place, has sequenced 214,000 genomes — almost 6 percent — of the country’s 3.7 million cases.
Unlike the United States, the U.K. invested in genetic sequencing early on in the pandemic, launching its genomics consortium in March with a $27 million investment and a multimillion-dollar boost late last year.
Other countries have dramatically higher proportions of cases sequenced compared with the United States because they have far fewer cases: The country with the highest rate of sequencing per case, Iceland, has analyzed 4,000 genomes out of 6,000 people who have tested positive.
‘Patchy’ U.S. program
Even before the emergence of mutations such as the variants first discovered in South Africa and the United Kingdom, U.S. experts had been warning for months about the need for a national standard for genetic surveillance.
In May, the CDC launched a surveillance program for the coronavirus called SPHERES (SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance). But, in practice, the program relied on a haphazard patchwork of academic labs contributing genetic sequencing on a volunteer basis.
A July report by the National Academies of Science said that “poor funding, coordination, and capacity” had led to a “patchy, typically passive, and reactive” U.S. sequencing effort.
“There weren’t funds to do it,” Hamilton said.
Last month’s stimulus bill included funding that could help ramp up genetic sequencing, health officials said. Biden administration officials said the president’s $1.9 trillion proposed spending plan also includes much-needed funding for genetic sequencing.
On Wednesday, Jeff Zients, coordinator of the White House coronavirus response, called the current state of U.S. sequencing “totally unacceptable.” In Biden’s proposed spending plan, he said, “we remedy that situation.”
But even without additional funding, many U.S. labs already have the basic machinery and expertise needed to do genetic sequencing, said Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security.
“In some cases, there are existing resources that just need to be reoriented,” she said. “The need for federal coordination is the biggest challenge right now.”
Many public health labs have recently begun sequencing or have partnered with academic institutions to do so, said Scott Becker, chief executive of the Association of Public Health Laboratories.
“Everyone is getting involved, but we need a standardized approach for how to do it, how to report it. We can’t have scientists coming at it from every which way,” Becker said. In a call with CDC officials Thursday, his group and others urged the federal government to streamline such processes, he said.
The work of sequencing can be painstaking.
New York Health Commissioner Howard Zucker described the process at the Wadsworth Center, a clinical laboratory run by New York state.
The center receives samples, taken by nasal swab, from hospitals around the state. Each sample requires about 48 hours to process. Zucker likened the process to scrutinizing every letter of every word in a book.
“If we find a different letter in the book, then we put that book to the side,” he said. Once a figurative pile of similarly set-aside books begins to grow, the state knows it has identified a cluster of related coronavirus samples.
Scaling up such efforts nationally would accomplish two things: It would create a pool of random samples, so experts can tell which variants are surging — along with where and among what demographic groups. But equally important, it would allow experts to home in on unusual cases so they can understand how different variants are behaving — whether they are deadlier, more transmissible or able to sidestep newly developed drugs and vaccines.
“We need to be able to tell when our best countermeasures are no longer effective, so that we have time to adjust them,” Rivers said.
In recent days, scientists in Denmark — which has one of the world’s most robust surveillance efforts — have said the British variant is spreading in their country at an alarming rate and isn’t responding to established ways of slowing the pandemic. Cases involving the variant are increasing 70 percent a week in Denmark, despite a strict lockdown, according to Denmark’s State Serum Institute, a government health agency.
“We’re losing some of the tools that we have to control the epidemic,” said Tyra Grove Krause, scientific director of the Danish institute. The country recently began sequencing every new positive coronavirus test to check for mutations.
British Prime Minister Boris Johnson last week suggested for the first time that the U.K. variant may be more deadly than the original virus. Because it can spread more easily, it can also quickly overwhelm medical systems, turning previously survivable bouts of the virus into perilous ones if hospitals are full and medical care is limited.
“It’s concerning that we don’t even know the extent of variants that currently exist in the U.S.,” Hamilton said. She pointed to the recent surge of cases in California, noting that without wider sequencing it’s difficult to know how much of that surge has been driven by people’s behavior and how much by the characteristics of some possibly unknown variant.
Limited sequencing efforts in the United States have already spied variants growing in our backyard.
Working with colleagues at Southern Illinois University, RNA biochemist Keith Gagnon recently sequenced what he believes is a new variant that has become especially prevalent in the United States.
The researchers named that variant 20C-US (the first number and letter designate the branch of the family tree from which the virus emerged; the US is for the country of discovery).
Their report describing the 20C-US variant has not yet been peer-reviewed. It seems to be substantiated by a separate study — also not peer-reviewed — that supports its findings. Another group of scientists at Ohio State University independently found a branch of that variant, which has taken on new mutations.
“It made sense the U.S. should have their own variant,” Gagnon said. “But of course, nobody knew.”
His team’s analysis suggests the variant appeared in the southern region of the United States in the late spring or early summer of 2020. The researchers found no signs that it is more harmful or deadly. Gagnon raised the possibility that 20C-US was more transmissible and had not spread by chance. But he stressed that this was a hypothesis, which he plans to test in lab experiments.
In the meantime, the country needs more sequencing to monitor such homegrown variants, he said.
“Genomic surveillance is probably the number-one thing, besides covid-19 testing itself, that we can do to track the virus,” Gagnon said. “Without it, we are flying blind.”
Harry Stevens and Joel Achenbach contributed to this report.
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