This is an excerpt of a 2,964-word article in the February 8, 2021 issue of THE DARK REPORT (TDR). The full article is available to members of The Dark Intelligence Group.
CEO SUMMARY: Variants of the COVID-19 virus are appearing across the world. Recent data show the same variants will infect people in several different countries. Here in the United States, interest is growing in variant sequencing by clinical laboratories with specimens from patients who test positive as a way to identify mutations and track their spread. Today, there is no reimbursement for labs that do this sequencing, but a new bill in Congress would establish payment for the genetic sequencing of specimens from patients with positive test results.
TESTING FOR VARIANTS OF SARS-CoV-2 is poised to become the next big thing for many of the nation’s clinical laboratories. Some labs have begun using next-generation sequencing (NGS) to identify mutations in coronavirus strains that may be more lethal or may spread more quickly than the original virus strain. When variants are identified, labs need to report the results to public health officials.
Earlier this month, the State Serum Institute in Denmark reported that cases involving variants of the SARS-CoV-2 virus were increasing at 70% a week among the Danish population. The Danes knew that SARS-CoV-2 variants were rising because they had been variant sequencing positive coronavirus specimens to identify mutations.
Given that Denmark has a population of fewer than six million, it was easier to do SARS-CoV-2-variant sequencing there than it would be in the United States, which has a population of 330 million. At the time, U.S. clinical laboratories were variant sequencing only 0.3% of positive cases, leaving physicians and public health authorities largely blind to the spread of the various SARSCoV-2 variants, according to reporting in The Washington Post.
Recognizing the pressing need to assess the spread of these variants, some forward-looking pathologists and clinical laboratory directors are already developing methods that use next-generation variant sequencing specifically to identify variants among patients who test positive. But these nascent efforts face at least three significant hurdles to find ways to run variant-sequencing efforts at scale in the midst of the coronavirus pandemic:
• A lack of payment,
• A shortage of the right equipment in most labs, and
• A shortage of staff.
To understand the hurdles that pathologists and clinical lab directors face when hunting for SARS-CoV-2 variants, The Dark Report interviewed Garret Hampton, PhD, President, Clinical Sequencing and Oncology at Thermo Fisher Scientific.
Hampton has more than 25 years of experience in precision medicine in oncology, cancer genomics, and companion diagnostics, using next-generation sequencing as a core tool.
Hampton explained how certain hospitals and health systems in the United States and other countries are sequencing COVID positive cases to identify variants. He noted that many observers believe most variance sequencing intended to identify variants of SARS-CoV-2 in patients who test positive for the coronavirus is being done almost exclusively in large reference laboratories.
While variant sequencing in central labs is the dominant approach, pathologists and clinical lab directors have shown strong interest in doing variant sequencing in local and regional laboratories closer to the physicians and patients they serve. Doing so would allow more labs to identify variants and trace their spread quickly.
Testing at the Local Level
“There is a need for SARS-CoV-2 variant testing that can help health officials track and control the outbreak in their communities,” commented Hamption. “We’ve seen the assumption that variant sequencing for COVID-19 is done predominantly in large reference labs and academic medical centers. But that leaves an important element unaddressed. That missing element is the need for local level sequencing for SARS-CoV-2 variants to expand at a faster pace than is currently true. That’s the key right now.”
Clinical labs in the United States would already have identified more SARS-CoV-2 variants except that few—if any—sources of payment exist for labs that sequence COVID-positive specimens for the purpose of identifyingvariants of SARS-CoV-2.
On Feb. 4, members of the U.S. House and Senate introduced legislation to boost U.S. efforts to track coronavirus variants, and the Biden administration has proposed funding to pay for that work. (See sidebar, “Federal Legislation Would Fund Sequencing of COVID Variants,” below.)
Further, many local and regional labs may lack the equipment and staff needed to do such sequencing at scale. Therefore, there is a growing need to encourage health insurers and the federal government to pay for such testing, Hampton said. The following is an edited presentation of Hampton’s interview with Donna Marie Pocius, IVD Reporter for The Dark Report.
EDITOR: Can you describe the work that Thermo Fisher’s laboratory clients are doing to identify variants to the SARS-CoV-2 coronavirus?
HAMPTON: Yes, certainly. But first, I’d like to step back just a bit to explain that currently almost all the genomes of the positive infections from the SARS-CoV-2 virus are being sequenced in two different lab settings in the United States, Europe, and in other countries.
EDITOR: How do the settings differ?
HAMPTON: One setting is comprised of the large reference labs, such as LabCorp and Helix Diagnostics. The other setting is made up of academic medical centers (AMCs). To a lesser extent, some hospital networks are doing this work too. In one program, the CDC has contracted with large reference labs and with other labs, such as those in AMCs, to sequence genomes. That’s important to know because the goal of some of these efforts is to sequence coronavirus genomes at scale.
EDITOR: How is Thermo Fisher tracking these developments?
HAMPTON: We’ve heard from our customers that those efforts are important because they give us a way to track and trace the various viral strains. And tracking and tracing viral strains is what they tell us they want to do at the local level.
EDITOR: We have seen that many labs are interested in tracking and tracing viral strains in the areas they serve. What is the goal of those efforts?
HAMPTON: From what we’ve seen, our customer labs want to perform surveillance at a local level so that they can identify variants that are known, or new strains that may be more impactful than the original strain. Once they have that data, they can alert local public health agencies and provide accurate and actionable information to those authorities.
EDITOR: How might labs flag specimens that would be candidates for sequencing?
HAMPTON: Several of our customers do this work now. For example, these labs know that—if they see an altered result via the SARS-CoV-2 PCR result for certain patients—that result indicates something is different from this specimen, compared to the original strain. Those are the specimens that they will sequence to identify any variants that may be present.
EDITOR: Are any of your lab customers doing this sequencing currently?
HAMPTON: One of our lab customers is pathologist Timothy Triche, MD, PhD, the Co-Director of the Center for Personalized Medicine Program at the Children’s Hospital Los Angeles (CHLA). At his lab, they sequence 100% of their COVID-19 PCR positive cases. As you know, Los Angeles County has had—and continues to have—high COVID-19 infection rates. They’re looking for variants and, not surprisingly, they’re finding that some of them are the same variants that labs in the United Kingdom have reported. We don’t yet know whether those variants tend to spread COVID-19 infections faster than other strains.
EDITOR: Are there other interesting findings from labs doing this gene sequencing?
HAMPTON: Another of our customers is the Cedars-Sinai Medical Center, which is also in Los Angeles. In that lab, they’ve identified a new strain called the California Strain, abbreviated as Cal.20C. This strain is thought to be more infectious than other strains and it’s actually been found in about a third of Cedar-Sinai’s positive patients. There’s speculation that this strain is contributing to the surge in cases there.
EDITOR: Have any labs that regularly do next-generation sequencing (NGS) for cancer testing started to use those capabilities to do variant sequencing of the SARS-CoV-2 coronavirus?
HAMPTON: Yes. We have labs that typically use NGS for tumor sequencing and are using some of those capabilities for COVID-19 sequencing. One of those labs is the Kabara Cancer Research Institute which is part of the Gundersen Medical Foundation in La Crosse, Wisc. They recently pivoted from doing cancer research to sequencing known SARS-CoV-2 positive samples from that region in Wisconsin. That work is interesting because they traced a single infection in a meatpacking plant in Northeast Iowa across three states over six weeks.
Following the migration of the individuals who had that strain into different states is important for anyone identifying a variant and then trying to understand the epidemiology of how that infection spreads.
EDITOR: Each of those cases are fascinating and worthy of further study. Have you had any customers identifying SARS-CoV-2 variants in other countries?
HAMPTON: Yes, we have two customers in Italy and one was among the first to tell us that they were able to find new strains with our technology and assays. Another customer was in Sao Paulo, Brazil, where the lab identified the first case of a COVID-19 reinfection in Sao Paulo. From these examples, you can see that there are a variety of different uses for variant sequencing among our customers.
EDITOR: As your lab customers seek to identify SARS-CoV-2 variants, have you seen a theme in the work they are doing?
HAMPTON: The central tenet that I see in these examples is that labs are looking for variants so that they can alert their public health authorities, and so that they can understand the prevalence of the variants in their areas. We see stories in the news that are similar to what we hear from our customers. Many of our lab customers want to know if they can do this sequencing at the local level and they want to know if they can do it quickly.
EDITOR: Is that evidence that interest in variant sequencing among labs is growing?
HAMPTON: Yes, and that’s the state of SARS-CoV-2 variant testing right now. We hear about large reference centers doing most of the variant sequencing for SARS-CoV-2, but the key right now is that there is definitely increased interest in doing more sequencing for SARS-CoV-2 variants at the local level.
Is your lab interested in variant sequencing for COVID-19? Please share the challenges you face with us in the comments below.