How COVID-19 Is Changing the Sequencing Landscape
By Allison Proffitt
April 20, 2021 | The United States lags behind at least 30 countries in terms of the sequencing it has done throughout the pandemic, according to data deposited into GISAID and reported by Nature. This is a bit surprising considering the breadth of US expertise and equipment
Thermo Fisher Scientific provides both NGS sequencing technology platforms as well as SARS-CoV-2 diagnostic tests with FDA early use authorization. From this vantage point, the company sees the range of pandemic-response testing, and Garret Hampton, President, Clinical Sequencing & Oncology at Thermo Fisher Scientific, sees a few reasons why sequencing is lagging.
“I think part of [the delay] was really how to coordinate—we have so many states here—how to coordinate sequencing at state and public health labs, through CDC etc. I think we in the United States were just very slow by comparison to other European countries to kick this off,” he told Bio-IT World. “It’s changed quite a bit now,” he added.
But after a slow start, Hampton now sees a growing diversity in the sequence generators, even if they face infrastructure challenges.
The largest central and diagnostics labs—Labcorp and Quest, he mentioned—already have sophisticated users of next-gen sequencing technologies, Hampton said, and they have infrastructure to share data and deposit sequences into international databases like GISAID.
But for smaller labs, this is new territory, and sequencing a viral genome and then sharing it widely—and securely—is not straightforward. “In some of the smaller labs, in some of the smaller hospital systems, public health labs, it’s probably been somewhat of a challenge to take the sequencing information and set up the informatics for them to deposit the sequencing,” Hampton explained. “There are quite a few fixes for that,” he acknowledged, but “you can’t necessarily go today and buy an app” to deposit your data in all of the right spots.
More widely distributed sequencing has been a trend over the past few years as sequencers have become cheaper, smaller, and more user friendly, but Hampton reports this trend has ramped up during the pandemic. The groups who have begun sequencing in the past 12 months are extremely diverse, he said.
“Now what we’re seeing in the environment, in general, is sequencing in various settings. Some are finding it a bit more difficult than others.”
On the very eve of the pandemic, in November 2019, Thermo launched the Ion Torrent Genexus System, which is “the only fully automated sequencer on the market,” Hampton said. The platform features an automated specimen to report workflow with 10 minutes hands-on time, two user touchpoints, and a turnaround time of one day. The system requires minimal amounts of tissue sample and can run small batches cost-effectively, the company says, to deliver a comprehensive report in one day.
The original target users for the Genexus platform were oncology labs, Hampton said, where clinicians wanted to do sequencing close to the patient and as quickly as possible. And Hampton says Thermo has seen some of these oncology labs switching to sequencing SARS-CoV-2 genomes. They are not abandoning oncology, but the pressures of the pandemic called for a pivot and these sequencing platforms were put to new use.
Others Genexus users are brand new customers who have used the pandemic—and the public funds associated with it—to finally launch sequencing programs. They said, “‘We have had a need for SARS sequencing today, but we’ve always had a long-term interest in sequencing for oncology applications,’” Hampton explained.
And finally: “During this pandemic, and once we started to see the variant strains, we had many new customers who became very interested in taking on Genexus in their labs so that they could get rapid strain identification and then alert their public health authorities in the various states that they were seeing a few of the patients… with these variants,” Hampton said.
User Needs Going Forward
Quantifying these user groups is going to be important, Hampton said, as Thermo and the sequencing industry move forward. He predicts that the sequencing volume and intensity will go down as the pandemic needs shift—but not completely.
After the current volume of SARS-CoV-2 sequencing goes down, “now we’re in a circumstance where it’s like central testing for flu. You’ve got to have some baseline capability,” he said. “COVID will always be here, but it’ll just be modified over time: modified in terms of infection numbers and vaccinations frequency and so forth. There’s always going to be a basal need.”
And then there will be new sequencers—and new skilled scientists—in labs that had not previously done sequencing. It’s an opportunity for many people to ask new questions and approach their work in new ways, Hampton said.
“If you sequence every nucleotide, you get tremendous insight into the biology,” he said. “The virus enters human cells via the spike protein. What we’ve seen with some of these strains is that some of the more infective ones bind with the spike protein much, much tighter to human cells. We had no idea that was the case!... This has been massively important to understand the biology of the virus and how the virus interacts with human cells,” Hampton said. “That’s now set off a lot of thinking around can we do this with other viral strains when they come?”
Hampton also reports new diagnostic questions. Now customers are asking for pan-respiratory panels, he said, to differentiate between flu A, flu B, COVID-19, RSV, and other viruses associated with respiratory diseases.
“Now we have a new weapon in our arsenal so that when we see diseases like this come to bear, we’ll be sequencing quickly because we have that set up in very different types of labs,” Hampton said. “When we see an outbreak, I think we’ll know fairly quickly what we’re dealing with, and if we understand the biology of these viral infections and the epidemiology from prior history, it’s going to really help us realize what’s important very quickly.”
It’s been a big adjustment for the labs and the teams acquiring sequencing capabilities, but Hampton believes it will pay dividends in public health.
“It’s a crash course. Now we’ve stepped up another level in terms of how we surveil and understand these viral infections. I think that’s a tremendous outcome!”