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 having clinical laboratories sequence 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 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 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 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 testing 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 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 Joseph Burns, Senior Editor 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?
“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.”
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.
EDITOR: One question many labs will ask is how do they get paid for sequencing SARS-CoV-2 variants? As you may know, many health insurers do not payfor COVID-19 testing for asymptomatic patients. Does that suggest that insurerswill balk at paying to sequence variants?
HAMPTON: I think that’s one of the biggest hurdles to doing large-scale genome sequencing of the virus. It’s different outside the United States. In Europe, for instance, government-run health systems in France and Germany are paying for variant sequencing at a specific rate. But here in the United States, insurers are not paying, because the value of variant sequencing is not immediately obvious to them.
Once the need for more variant sequencing is widely known, and variants become more visible, there will be heightened awareness about the need. Also, I’m hopeful that the government will step in at some point in part because I don’t think anybody expected to see the numbers of strains we’re seeing.
EDITOR: One researcher estimated that the SARS-CoV-2 coronavirus was mutating at a rate of about two variants per month. If correct, does that mean that, after 12 months, the world now has about 24 extant variants, or is it more or less than that number?
HAMPTON: That number is probably not too far off. Today, we know of a variety of strains. There’s what is being referred to as the Brazilian Strain, the South African Strain, the UK Strain, and the Los Angeles Strain to name just a few. The sheer number of infected people in the world leads to that kind of a detectable mutation rate. When you have numbers like we’ve seen worldwide, then you start to see a wider variety of variant strains.
“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 COVID-19 variants at the local level.”
EDITOR: The other challenge for pathologists and clinical labs is that they need the right equipment and staff to identify SARS-CoV-2 variants. How do labs solve those problems?
HAMPTON: Here at Thermo Fisher, we have been working to make sequencing easier for clinical labs working with the Ion Torrent Genexus System that we introduced in November 2019. The Genexus is the first fully integrated NGS platform that includes an automated specimen-to-report workflow that delivers results in a day.
EDITOR: What do clinical labs need to know about developing this capability?
HAMPTON: At the time we developed our Genexus System, and continuing today, we saw a need in oncology for the decentralization of testing to make testing easier, faster, and simpler. Because most labs taking on this work may not be sophisticated users of NGS, we had to develop something that’s fully integrated and has a short hands-on time. We did that on purpose because laboratories want results, and that means it’s not about the machine necessarily. It’s about getting results from your lab quickly.
EDITOR: So, the Genexus System solves some of the problems pathologists and clinical labs face when they prepare to sequence for SARS-CoV-2 variants. But where do they find the clinical laboratory scientists to run these machines?
HAMPTON: Up until now, most NGS has been done in bigger, sophisticated labs, such as those in academic medical centers or in large hospital systems. In those labs, the staff has done sequencing before and the senior staff fully understands sequencing. The senior staff have also hired the technicians or trained their lab techs to do NGS for cancer or for other testing. We saw that pattern clearly and wanted to get NGS beyond those settings alone, to make gene sequencing available to smaller labs and smaller local hospitals. NGS can’t be and shouldn’t be just in the realm of the AMCs or the larger hospital systems. It has to be done in more local and regional lab settings.
“We saw that pattern clearly and wanted to get NGS beyond those settings alone, to make gene sequencing available to smaller labs and smaller local hospitals. NGS can’t be and shouldn’t be just in the realm of the AMCs or the larger hospital systems. It has to be done in more local and regional lab settings.”
EDITOR: How has Thermo Fisher addressed this need for smaller clinical labs?
HAMPTON: Our premise is that we offer equipment for NGS that does not require a lab to hire highly trained technicians. That’s a huge cost for most labs. We want labs that can take an immunohistochemistry technician, for example, and have that person also do genetic sequencing. That’s how we view it, and we’re approaching that level in terms of the value proposition and ease-of-use of our NGS equipment. Labs want to do this sequencing for more patients. They just need the equipment to do it with a certain level of ease of use.
EDITOR: Assuming that more clinical laboratories will be able to start sequencing for SARS-CoV-2 variants, what do they do with that data? First, they would report it to local or state health authorities, but where else would they report that data?
HAMPTON: There are repositories for this data. One of them is GISAID [Global Initiative on Sharing Avian Influenza Database] at www.GISAID.org. This initiative promotes the rapid sharing of data from the SARS-CoV-2 and influenza viruses. This includes genetic sequences and related clinical and epidemiological data associated with human viruses and geographical and species-specific data associated with avian and other animal viruses. That data is designed to help researchers understand how viruses evolve and spread during epidemics and pandemics.
EDITOR: Besides GISAID, are there other places that clinical laboratories doing SARS-CoV-2 variant sequencing can report their data?
HAMPTON: That’s a more difficult question to answer. It could be that state public health labs will need to develop the ability to collect and publish local SARS-CoV-2 variant sequencing data.
EDITOR: Thank you for taking the time to update our clients and regular readers about the latest developments in variant sequencing of SARS-CoV-2.
HAMPTON: The identification of variants is an important new development that affects how clinical labs respond to the pandemic. Thanks for the opportunity to share this information.
Contact Garret Hampton at 413-237-5141.
Federal Law to Fund Sequencing of Variants
SOME MEMBERS OF CONGRESS RECOGNIZED THE NEED TO ESTABLISH PAYMENT to clinical laboratories that are gene sequencing SARS-CoV-2 to identify variants. On Feb. 4, U.S. Senator Tammy Baldwin (D-Wisc.) and U.S. representatives Ami Bera (D-Calif.) and Scott Peters (D-Calif.)introduced a bill to boost efforts in clinical laboratories to identify and track variants to the SARS-CoV-2 coronavirus.
In announcing the bill, the members of Congress said the United States was conducting sequence-based surveillance of only about 0.3% of COVID-19 cases, and that our nation’s efforts lagged behind that of other nations. “It is critical that the United States scale up its efforts to survey at least 15% of cases to better grasp new and emerging variants, understand their origins, and develop mitigation strategies,” the lawmakers said. “The virus has changed, and it will continue to change as more Americans are vaccinated.”
In the same announcement, the members of Congress said the Biden Administration’s proposal, called the American Rescue Plan, addresses the need to identify emerging strains of SARS-CoV-2. Further, the plan includes funding to increase sequencing, surveillance, and outbreak analytics.
Also, they added, the Tracking COVID-19 Variants Act would provide $2 billion for the Centers for Disease Control and Prevention to support a national sequence-based surveillance program.