“There are definitely states where they really champion this,” said Duncan R. MacCannell, chief science officer for the Centers for Disease Control and Prevention’s Office of Advanced Molecular Detection. “But, you know, there’s also a lot of blanks [on the map], dark spots, places where we just don’t have regular sequence data.”
In the D.C. region, Maryland stands out for dramatically enhancing its search for variants, attempting to more than double its output and detect new versions as they emerge. Nationwide, sequencing volume has tripled since early February, but the country had been so far behind in its efforts that CDC and public health experts say nearly all states still need far more sequencing to create an accurate picture of variants already circulating.
The uneven information about variants circulating in the country comes as states race to vaccinate residents ahead of a potential fourth surge in cases fueled by more contagious and potentially more deadly variants. The Biden administration has put nearly $2 billion into helping the CDC ramp up variant surveillance efforts nationwide, including $1.75 billion included in the rescue package Congress passed last month.
MacCannell’s division leads the consortium to coordinate the country’s knowledge about variants, as well as recruits private labs and universities to surveil for them. Part of the challenge, he said, is that not all public health labs have the expertise to decode the genetic sequences deposited into the national database and then connect them to community outbreaks.
“Ironically, last year, we actually planned to roll out enhanced training for molecular skills for state and local public health departments, epidemiologists,” MacCannell said. “But that was somewhat derailed by the pandemic response.”
Public health experts and epidemiologists hope the nation’s growing system can quickly spot emerging variants before they gain a dangerous foothold.
“We’re making great progress. I still don’t think we are where we want to be or need to be,” Janet Hamilton, executive director of the Council of State and Territorial Epidemiologists, said in an interview late last month. “We still have quite a few gaps in how the data is shared and how rapidly it’s shared. We still have labs that are conducting sequencing, and their data is not necessarily incorporated as part of the national picture.”
Maryland has had a sluggish start compared with West Coast states such as California and Washington, where private labs and universities have conducted surveillance since near the beginning of the pandemic.
But in March, after the federal government began sending states cash to help sequencing efforts, Gov. Larry Hogan (R) set a goal to sequence 10 percent of all positive coronavirus tests moving forward, a threshold some experts say is critical to detect both newly emerging variants and those known to be concerning.
Some states, such as Oklahoma and South Dakota, have sequenced less than 0.25 percent of their positive tests since the pandemic began, according to CDC data. In places with low rates, those efforts are largely done by private commercial companies such as Quest Diagnostics and LabCorp that have contracts with the CDC to do 6,000 sequences a week nationwide.
The best performing states, including Washington and Maine, have done more than 3 percent of their positive cases since January 2020. Virginia has done 0.88 percent and Maryland has done 1.46 percent; D.C. data was not available.
While it takes a few hours for a well-trained lab technician to determine if a sample has the virus, sequencing that same sample calls for more sophisticated machinery and a highly trained scientist to then make sense of the virus’s genetic sequence, which is 30,000 nucleotides long. Sequencing work takes days, and Maryland has built a multipart operation involving a mix of university, public health and private labs to get enough samples screened.
A year ago, the genomics lab at the University of Maryland School of Medicine could have started sequencing coronavirus samples and searching for variants on a significant scale, if only there had been the money to launch it.
“Because of the lack of funding, because it’s not a very cheap enterprise to stand up, we basically never pursued it,” said Jacques Ravel, associate director of the school’s Institute for Genome Sciences. “There was no major interest in doing sequencing, unfortunately.”
Now that variants have spread widely and sparked deep concern about prolonging the pandemic, Ravel’s operation is in high output helping Maryland join the many states dramatically ramping up the search for versions of the virus that could spread faster, make people sicker or evade the vaccines designed to immobilize it.
Some of the state’s preliminary data, particularly around the variant first identified in the United Kingdom, is concerning.
The CDC announced last week the more transmissible and potentially more lethal variant had become the most prevalent version of the coronavirus in the United States. While it is less widespread in Maryland, D.C. or Virginia than in places such as Michigan, Maryland’s robust surveillance program shows it’s quickly on the rise: Two weeks ago, about a quarter of the 200 samples tested weekly in Ravel’s lab had the variant. As of Friday, the latest data showed it had risen to 38 percent overall, with as much as 60 percent of positive samples from a community testing site in Baltimore City, where the coronavirus case rate has risen sharply in recent weeks.
That threshold is potentially alarming.
“What we know from the experience of half a dozen countries — the first wave of countries that were really hit by the British variant — is that when the variant passed 50 percent of the variants being sampled, it really took off,” said Jonathan “Jono” Quick, a public health doctor with the Rockefeller Foundation and author of “The End of Epidemics.”
“The thing is, you don’t get a do-over,” Quick said. “You can’t catch up. I mean, once you get a surge start happening, then it takes a herculean effort to turn it around.”
Maryland’s surveillance operation, like those in many states, also relies on private companies such as LabCorp and Quest to churn out sequences for some of their positive samples. Ravel’s lab, which contributes about a quarter of the state’s weekly goal to sequence 800 positive test samples, gets paid via a state contract for depositing at least 200 sequences each week into national and international databases tracking how the virus evolves. Another quarter of the state’s sequences come from a researcher at Johns Hopkins Medicine in Baltimore, who had been doing genomic surveillance since the pandemic began.
“Frankly, it requires a lot of collaboration,” said Clifford Mitchell, director of the Environmental Health Bureau in the Maryland Department of Health. “This is the kind of thing that doesn’t happen in one institution.”
Heba Mostafa, assistant professor of pathology at Johns Hopkins Medicine, had been using her research grants to finance genetic sequencing since March 2020, culling samples from the organization’s extensive patient network to track how the virus has changed. In early January, the variant identified in the United Kingdom showed up in less than 2 percent of her samples, she said. By early March, it was in 35 percent.
It wasn’t until March that her lab began working with the state to streamline and share data among labs searching for variants.
Virginia and D.C. officials say their jurisdictions have also ramped up sequencing efforts. Each relies on a mix of public and private labs without centralized coordination to boost the number of samples sequenced. Neither jurisdiction was able to estimate what share of their positive tests are currently sent for sequencing.
“It really is kind of tricky to get your arms around the total number,” said Jenifer Smith, director of the D.C. Department of Forensic Sciences.
D.C.’s public health lab began focusing on variant testing in December. As of early March, the city’s lab had sequenced 236 virus samples total, and sent 50 more to the CDC to sample. D.C. asked each of the city’s hospitals to send in five positive coronavirus samples per week for testing.
In Virginia, the Richmond-based state lab, known as the Division of Consolidated Laboratory Services, started sequencing coronavirus samples in March 2020, the month residents began testing positive for the virus.
Much of the early sequencing work was done to simply characterize the virus and track outbreaks to determine the spread. That meant looking at viruses in specific nursing homes, correctional facilities and other group settings.
“We really wanted to be able to pinpoint if there were any mutations or anything arising that could cause greater transmission or more severe illness,” said Logan Fink, bioinformatics lead scientist for the state lab.
The effort has morphed into a targeted surveillance effort to detect the presence of variants in a community, quickly do contact tracing and make sure an infected person is in isolation, said Denise Toney, director of Virginia’s laboratory services.
The state lab sequences as many as 200 samples per week, culled from 1 percent of positive tests from commercial testing companies and samples sent to its own lab. A recent federal grant will enable the lab to double its sequencing capacity.
Amy J. Mathers, an associate professor of medicine and pathology at the University of Virginia School of Medicine, said her lab began genome sequencing in February after learning the value of the process from scientists in the United Kingdom.
Her work began with a pilot program focused on University of Virginia students, and she is now negotiating with the state to sample 250 sequences a week.
Kelly Wroblewski, director of infectious-disease programs at the Association of Public Health Laboratories, said scientists are working blind in a lot of ways because they have evidence from only one year of the pandemic, when a lot of public health orders have been in place, compared with hundreds of years of evidence about the flu. It will take time to know if people will need booster shots or if the vaccine should change to accommodate variants, she said.
“The most important thing to be concerned about is getting the vaccine,” she said. “I understand people want answers and they want to know,” but, Wroblewski said, the science is informing mitigation strategies based on what is known at a particular time and that can change. “A year in the life of any microbe is not a very long time.”
Steve Thompson contributed to this report.