Weeks after the first case of a more infectious strain of the SARS-CoV-2 virus was detected in Orleans Parish, the Louisiana Department of Health appears to be planning to scale up the state’s capacity to genetically sequence COVID cases.
Administrators at LSU Health Sciences Center-Shreveport and LSU’s Pennington Biomedical Research Center say that LDH has reached out in the past month to discuss a sequencing partnership, and has even helped purchase key technology.
Kevin Litten, a spokesperson for LDH, said that the agency was “currently researching the best ways to partner with local labs for additional sequencing but no final decisions have been made.”
According to Louisiana researchers who have sequenced COVID-19 cases during the pandemic, the state’s ability to monitor for concerning variants has been hampered by a lack of federal resources.
“Unfortunately, there hasn’t really been a formalized line of funding for sequencing,” said Christopher Kevil, the vice chancellor for research at LSUHSC-Shreveport. “LDH knows that, and they’re helping to correct that, so that we can get the fuel to do the sequencing. And that fuel is money.”
Between the two possible LSU initiatives, the state’s sequencing capacity could increase by hundreds of samples a month.
The Centers for Disease Control and Prevention recently increased the number of sequences it would process on behalf of the states, and LDH is now sending about 22 samples every two weeks to the CDC for sequencing, a number that is determined by Louisiana’s population.
That partnership ended up identifying the first case of the British variant in the New Orleans area, and two more cases in Louisiana that were announced Thursday afternoon.
LDH looks in part for samples that show preliminary signs of being variants. (Many PCR tests check for three different genetic markers of the virus, but because of a mutation, the more infectious British variant, called B.1.1.7, only shows up positive for two of the three markers.)
The problem with the scope of that sequencing, said Jeremy Kamil, a virologist at LSUHSC-Shreveport who has spearheaded much of the university’s sequencing work this year, is that it can’t tell public health officials about the prevalence of different strains, or about new mutations.
If the US focuses on samples that appear to be B.1.1.7, Kamil said, “that prevents you from finding other variants. There could be homegrown variants here that are growing just as fast as B.1.1.7.”
“If you’re only looking for B.1.1.7, well, that’s like a drunk looking for their keys under the lamppost.”
Kamil and a number of other virologists interviewed agreed that the state’s target should be to sequence 10 percent of all new COVID cases in the state.
“The reality is [10 to 20] samples are not enough,” said Kevil. “Most importantly, you’ve got to make sure that you’re getting a wide coverage of specimens across geographic and demographic areas.”
As of Friday, 2,629 Louisiana sequences have been uploaded to GISAID, a widely used international sequence-sharing platform. That’s about .8 percent of all 345,457 confirmed COVID cases in the state. Most of them were sequenced by the LSUHSC-Shreveport lab, using its existing budget with no additional government funding.
What’s in a strain?
At a press conference Thursday afternoon, Joseph Kanter, who is heading the state’s coronavirus response for LDH, acknowledged that the British variant was likely widespread in Louisiana.
“[The country’s low sequencing capacity] creates an iceberg scenario,” Kanter said. “We should all assume that there is significantly more of the UK variant circulating in this state than has been identified so far.”
Globally, there are three strains of coronavirus that appear to be about 50 percent more infectious than the baseline. All are circulating in a number of different countries, but are commonly known as the British variant, the South African variant, and the Brazilian variant, based on where they were first identified. The three emerged independently, but share key mutations.
Last week, the UK government suggested that the British variant could also be 30 percent more deadly than previous strains, although the country’s overwhelmed hospital system may also be contributing to the higher fatality rate.
The Brazilian strain, says Robert Garry, a virologist at Tulane University, is actually “the most dangerous of the variants,” because of evidence that it’s readily able to reinfect people who’ve already recovered from COVID. Recent evidence also suggests that some vaccines are less effective against the South African variant.
So far, only the British variant has been detected in Louisiana, although the other variants have been detected elsewhere in the United States.
However, Gov. John Bel Edwards said at Thursday’s press conference that he expected to see cases in Louisiana soon. “It’s very likely that they will move across the country at some point.”
Hundreds more sequences a month
Two LSU campuses are in talks with LDH to partner on sequencing work.
LSUHSC-Shreveport recently purchased a NovaSeq 6000 sequencer, which will allow it to process cases in-house. The details of that purchase “was a little complicated, I’ll put it that way,” Kevil said. But LDH contributed to the purchase. “Those machines aren’t cheap, and they’re pretty intense.”
Asked on Thursday for additional information on the purchase, LDH directed The Lens to file a public records request. A request was pending as of Friday morning.
However, the sequencing ramp up comes in the wake of the December federal COVID relief package, which included $19 billion for state and local COVID response. According to Kamil, the CDC has specifically encouraged state health officials to use that money for sequencing partnerships.
“We’re looking at hopefully the next five to six weeks to ramp up,” Kevil said. “But just like with the testing, you run into some snags.”
The lab, which contracts with LDH for testing in nursing homes and other congregate facilities in the region, would begin sequencing every positive case that came through its doors. And it’s in discussions to partner with LDH “to help them with their sequencing needs,” said Kevil.
LSU’s Pennington Biomedical Research Center already has the expensive machines and the technical expertise to perform the sequencing in-house, said John Kirwan, the center’s executive director.
“We haven’t been doing the sequencing work,” he said, “Because we didn’t have the funds to do it, and it wasn’t as high a priority until a few weeks ago, really.”
He said that the center has discussed a sequencing plan with the state.
“It hasn’t been finalized, but the expectation is that we would conduct sequencing on a monthly basis here.”
Although the agreement isn’t done, Kirwan said that the Center is “reprogramming our sequencers and gearing up for that.”
‘We’d be able to start that in a matter of weeks,” he said. The sequencing effort would be conducted by existing Pennington staff, and would likely aim to process hundreds of tests a month.
It’s not yet clear if any New Orleans-area labs would participate, although Tulane University also has in-house sequencing capacity.
Bad foundations
In the United States, genetic sequencing has been put on the backburner because diagnostic testing has been so scattered.
“Sequencing across the United States is bad,” said Rebecca Christofferson, a virologist at LSU-Baton Rouge whose lab processed hundreds of early COVID sequences. “We ranked 43rd in the world. We’ve done less than 100,000 sequences for almost ten million cases.”
Still, Louisiana has managed to sequence a large number of its positive cases relative to other states, Christofferson noted. About three percent of all COVID sequences in the US come from Louisiana, which makes up about 1.5 percent of the US population. As of January 25, the state had sequenced more COVID cases than university-heavy Massachusetts.
But that’s been driven by the time and resources of individual labs, not a coordinated government effort.
In the spring wave of the pandemic, when New Orleans was badly affected, Garry’s lab at Tulane began sequencing samples through its longstanding collaboration with a lab at Scripps Research Institute in California.
Garry and his collaborator at Scripps, Kristian Andersen, have federal grants to study emerging infectious diseases, and were able to shift some of that money to COVID.
“When the pandemic spread here, a lot of students in my lab volunteered to put their own projects aside,” he said. “But as the pandemic has dragged on, they need to get back to their own work,” although the lab has continued to forward a few cases along to Scripps.
In April, Christofferson’s lab picked up some of that work, sequencing cases from the Baton Rouge area, as an outgrowth of its work setting up a mass testing facility in March.
Like Garry, though, much of the work was done pro bono. A private company called Gingko Bioworks offered to sequence samples for free, in order to validate its own technology. But “it’s not a small thing to get samples prepared and shipped,” Christofferson said.
“We were doing [sample preparation] for free. My grad students graciously agreed to help with that.”
But after a month without funding, she said, her researchers had to return to their own projects — her lab normally focuses on emerging mosquito-borne viruses, like Zika.
Since then, the vast majority of sequencing in Louisiana has gone through the Emerging Viral Threat lab at LSUHSC-Shreveport. ““Around mid-summer,” Kevil said, “We understood that there would be variants of this virus, and that the real way to determine that was to sequence your viral positives.”
“And more importantly, it’s historically been the case that when you have a vaccine, you’ll have viruses that will escape that immune suppression,” he said. “And those are the things that you definitely need to sequence, because then you can identify them and modify the vaccine.”
As of this week, the EVT lab had produced about 70 percent of all sequences in the state.
LSUHSC-Shreveport has mostly footed the bill. Kamil mostly works with a Pittsburgh-based biotech company called MiGS for the sequencing itself. Each sample costs $200 apiece, though. By the end of August, he said, “we ran out of money, and there was no interest in it.”
“We’ve applied for money from the CDC, but got nothing,” Kamil said.
He resumed sequencing in December using internal money, once it became clear that the British variant posed an immediate threat. He’s also secured $100,000 in funding through Fast Grants, an organization that supports academic COVID research.
“But I view it as sort of a failure,” Kamil said. “This is important to all Americans, so the federal government should be involved.”