Only 0.02 percent of Tennessee's cumulative positive samples — 153 cases — have been sequenced for variants, according to data as of Feb. 12 from the National Genomic Surveillance Dashboard on the U.S. Centers for Disease Control and Prevention website.
"At this point, we literally are just flying blind," said Elizabeth Forrester, a research scientist at the Baylor Esoteric and Molecular Laboratory at Baylor School in Chattanooga. "The reality is that we don't even really know what's here."
The highly contagious B.1.1.7 coronavirus variant confirmed in Hamilton County this week likely circulated in the Chattanooga region for months before being detected, and researchers believe other dangerous variants could be here as well. Not only is Tennessee behind other states at sequencing to understand the spread, but the U.S. as a whole is far behind where experts say it should be in monitoring for variants, posing a threat to recent gains made to curb the pandemic even as vaccine supplies increase.
Despite being home to the most COVID-19 cases in the world, the U.S. has conducted genetic sequencing — the technique used to confirm a viral variant — on only about 0.38 percent of its COVID-19 samples, according to the CDC dashboard.
South Dakota and New Jersey have a similarly low sequencing rate to Tennessee's. The top states, Hawaii and Maine, have sequenced 3.5 percent and 2.5 percent of cases, respectively.
New variants are the result of mutations, which are random errors that occur in the genetic sequence when a virus replicates. It's normal for viruses to mutate. That's how SARS-CoV-2, the virus that causes COVID-19, came to be in the first place.
Most mutations don't benefit the virus, but every once in a while, a mutation crops up that gives the virus an advantage.
In the case of the U.K. variant, which was officially confirmed in Hamilton County through testing at Baylor — a mutation made the virus at least 50 percent more transmissible and may be associated with an increased risk of death.
Since Baylor first identified the variant, Forrester said it's showed up in the lab's COVID-19 samples with increasing frequency. The lab only analyzes a fraction of the area's coronavirus tests and has found at least 12 cases, with six of those cases occurring this month.
Another variant of concern that has been identified in 10 states, B.1.351, was first discovered in South Africa. The variant appears to evade the immune response — at least to some extent — from existing vaccines.
P.1, commonly called the Brazilian variant, is a third variant of concern that has so far been identified in four states.
Sequencing on a large scale allows scientists and public health officials to monitor changes in the virus over time. Beyond helping to identify new variants, it can help contact tracers identify possible chains of transmission and answer questions around whether certain strains cause more severe illness.
Gigi Gronvall, a senior scholar at the Johns Hopkins Center for Health Security, said that if you're not looking for variants, it will be much harder to know when new mutations are better able to evade vaccines and when to change or tweak vaccine strategy.
"We don't know what other potential characteristics COVID could take on, and we're certainly giving the virus lots of opportunities to evolve in different ways," Gronvall said. "We have to continue to monitor it. That's why we do the surveillance."
Bill Christian, a spokesperson for the Tennessee Department of Health, said via email that the state is in the process of implementing sequencing for SARS-CoV-2, the virus that causes the disease COVID-19. Although that will increase Tennessee's surveillance capacity, sequencing takes more time and resources than normal diagnostic testing used to determine whether someone has COVID-19.
"The addition of sequencing on top of current test loads for labs is considerable," Christian said. "Additionally, not all positive tests have enough leftover specimen for sequencing, and many labs don't perform sequencing. So transporting the specimen to a sequencing lab, RNA extraction and sequencing, and performing the bioinformatic analysis all take time."
Because the process is so slow, Christan said there's a delay between the identification of a positive specimen and the sequencing results.
"Even if the number of specimens being sequenced is drastically increased, those sequences may not be publicly available for weeks afterwards," he said.
Sequencing turnaround needs to be faster to have maximum impact, which is why Baylor's research scientists are working to bring that capability to the Chattanooga region.
"This is a piece of public health that's really important to kind of get started on, and I think it's also important for people to know how little we know in Tennessee," Richards said.
Gronvall, at Johns Hopkins, said that part of the reason why sequencing in the U.S. is lagging is because it's not traditionally seen as a public health tool.
"It was seen more as a research tool," she said. "This has been used for public health identification for foodborne illness, but not for this kind of respiratory disease."
Although some academic institutions have been sequencing the virus throughout the pandemic, there was no coordinated strategy, Gronvoll said. However, she believes this kind of genomic surveillance is the "wave of the future" when it comes to tracking viruses.
"I think it's going to be a big deal, not just for SARS-CoV-2, but for other diseases," she said. "This is not going to be the last new virus that affects people."
Forrester said Baylor is able to bring this more sophisticated surveillance to the Chattanooga region, but needs community partners to participate. Although the lab already tests some COVID-19 samples from local providers, researchers would need more in order to sequence at a meaningful scale. They would also need providers who are interested in sharing patient data and contact tracers to help identify chains of transmission.
"There has to be more of this overlap between research and the clinical world," she said. "We have all the pieces in place, and we hope that that will be one of the good outcomes of the pandemic — to connect those worlds."
Funding is a major challenge when it comes to increasing sequencing capacity. Although Baylor is committed to get things underway, it costs the lab $300 per sample in supplies alone, and that's after working to get the cost down.
The Biden administration on Wednesday announced that the CDC will invest nearly $200 million to expand genomic sequencing capabilities, and some lawmakers are vying to put billions more toward the effort.
Most sequencing is farmed out to bigger labs, but Forrester said in this case, Baylor's small size is an advantage.
"With these bigger labs, a lot of times there's a disconnect. When they get the sample, they have no idea why that sample was sent to them, who the ordering physician was," she said. "Because we are really small and community-focused, we can have those conversations about how a particular sequence may connect to a patient's outcome."
Regardless of what new information comes from the sequencing efforts, Gronvall emphasized that variants do not render COVID-19 tests and vaccines useless. Tests are still able to detect the presence of the virus, and even if some vaccines are less effective at preventing infection against certain strains, they still vastly reduce the risk of hospitalization and death.
"Right now, we're at such a critical point where vaccination can protect somebody from [the variants]," she said. "We know that [B.1.1.7] is more transmissible. It's going to put a stress on health care systems, so anything we can do to increase the vaccinations and decrease the spread is really a good idea."
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