Some lab experts advise that clinical laboratories and pathology practices should also plan on delayed payments for COVID-19 testing for uninsured patients
Regardless of whether infection rates for SARS-CoV-2 continue to wane or perhaps surge again, business changes are coming for staff at clinical laboratories and anatomic pathology groups. Forward-thinking lab administrators will want to evaluate post-pandemic strategies for labs to stay ahead of potential legal issues and keep their organizations financially healthy.
The public health emergency stemming from COVID-19 is set to expire April 16. That deadline could be extended. However, the U.S. Department of Health and Human Services (HHS) is under pressure from some circles to end the public health emergency, which would affect some health insurance provisions and potentially rein in relaxed rules for telemedicine.
“If you’re a laboratory, now is the time you need to start buttoning up [the above] concerns. You don’t want to be at the mercy of a quick cutoff,” said Jon Harol, president of Lighthouse Lab Services in Charlotte, N.C. The company hosted a webinar last week called “Preparing Your Clinical Lab or Pathology Practice for Post-COVID Success.”
Pathologists and clinical laboratory leaders should consider post-pandemic strategies for labs in the following areas:
COVID-19 testing for uninsured patients;
Preparations for government audits of SARS-CoV-2 tests performed during the pandemic; and,
Repurposing PCR equipment used for COVID-19 testing into other areas of clinical diagnostics.
These strategies will be explored further during the Executive War College Conference on Laboratory and Pathology Management, which takes place April 27-29 in New Orleans. Leaders of innovative clinical laboratories will share how their lab teams are helping to improve patient outcomes while encouraging health insurers to pay them for this value.
COVID-19 Testing for Uninsured Patients
On March 22, the U.S. Health Resources and Services Administration (HRSA) announced that its COVID-19 Uninsured Program stopped accepting claims for testing and treatment due to lack of sufficient funds. This development affects 8.6% of the nation’s population that doesn’t have medical insurance, according to the U.S. Census Bureau.
For clinical laboratories, the announcement could lead to delayed payments for COVID-19 tests performed on uninsured patients, said Mick Raich, President of Revenue Cycle Management Consulting at Lighthouse Lab Services, who also spoke during the webinar. Medical laboratories and pathology groups should anticipate reimbursement gaps and how that might affect revenues collected from payers.
“The patient relationship is going to be the most important thing. That puts labs at the head of the table,” says Jon Harol, president at Lighthouse Lab Services.
“Labs are going to do the testing and are going to bill for it, and there will probably be some retroactive payment,” Raich explained.
With midterm elections happening this year, don’t be surprised to see HRSA funding reinstated for COVID-19 testing for uninsured people, commented Robert Michel, Editor-in-Chief of The Dark Report and Founder of the Executive War College.
“We’ll have to wait and see. After all, it is an election year, so the representatives and senators in Congress would like to be re-elected,” added Michel, who also presented during the webinar.
“It is reasonable to assume that members of Congress don’t want to disappoint the clinical laboratories that stepped up to the table in the earliest days of the pandemic and have done huge volumes of COVID-19 testing.”
Preparations for Government Audits of Pandemic Testing
Another post-pandemic strategy for labs: Prepare for audits of COVID-19 test claims from the HHS Office of Inspector General (OIG).
Ahead of any OIG action, labs should consider performing self-audits to determine whether they complied with HRSA requirements. “The best thing you can do is go back and look at the first two months of your billing. Do an audit to ask: Did we bill anybody with insurance by accident?” Raich suggested. “Take a hundred of those claims and audit them.”
If a medical lab finds problems with uninsured COVID-19 billing, it may be prudent to self-report those discrepancies to the government rather than ignore them. “That looks a lot better to the OIG than tucking the stuff in a desk drawer and waiting for someone to knock on your door,” Raich noted.
Harol predicted the OIG will also review another aspect of how COVID-19 test claims were coded. Auditors will want to see if PCR test claims coded for higher reimbursement if the results were reported within 48 hours actually met that requirement.
“I expect that we’ll see auditing of the coding that was used. Under COVID, you got paid more if you were running tests on a high-throughput platform. It was almost an honor system there. I don’t know that I’ve seen much outside verification of that,” Harol explained. “I’m curious to see if there will be OIG pushback and more documentation required to prove the code was correct.”
Repurposing PCR Equipment Used for COVID-19 Testing
When the pandemic finally winds down, there will be less demand for COVID-19 testing, which could leave PCR equipment collecting dust unless labs make plans now on how to repurpose those systems.
“If you have a PCR instrument that can be revalidated, you want to start thinking about putting in a panel that tests for UTIs, sexually transmitted diseases, respiratory diseases, or women’s health,” Harol explained. “Those types of tests can be done on the equipment that a lot of COVID testing was being performed on, and it can be performed by the same scientists with that same skillset. That’s the low-hanging fruit.”
The next step is more complicated: Moving into the future, clinical laboratories need to determine what menu of tests will meet the needs of patients who previously submitted COVID-19 specimens for testing.
“The patient relationship is going to be the most important thing. That puts labs at the head of the table,” Harol continued. “How can you market your laboratory services directly to patients who might be interested?”
Watch for Developments in Telemedicine
Any post-pandemic strategies for labs will be influenced by how state governments and federal health officials regulate telemedicine in the future.
Pathologists and clinical laboratory directors should keep their eyes on whether telemedicine rules revert to more onerous requirements once the public health emergency lifts. Before the pandemic, rules for physicians licensed in one state generally limited when they could practice over state lines through telemedicine.
“In response to the pandemic, both the federal government and the states relaxed many prohibitions on the practice of medicine across state lines. This is significant for pathologists,” Michel said. “There is speculation that once government officials let this genie out of the bottle regulatory-wise, they won’t be able to put it back in. Thus, there are many predictions that officials at the state and federal level will be under pressure to retain the newer telemedicine rules after the pandemic has ended.”
Telemedicine proved to be a big benefit for Medicare patients during the pandemic. A report from HHS in December indicated telehealth visits in 2020 for Medicare beneficiaries increased 63 times, from approximately 840,000 in 2019 to 52.7 million. That fact should catch the attention of clinical lab managers and pathologists who want to keep their labs at the front edge of clinical services. For Medicare beneficiaries who see their physicians virtually, labs need the capability to access that patient so as to collect the samples needed to perform those tests ordered by the physician during the telehealth consultation.
Clinical laboratory scientists should also know experts warn that ‘herd resistance’ is more likely than ‘herd immunity’ due to low vaccination rates in many parts of the world
Scientists estimate 73% of the US population may be immune to the SARS-CoV-2 omicron variant. Whether the nation is approaching “herd immunity” against the disease, however, remains open to debate, the Associated Press (AP) reported. These estimates are relevant to medical laboratories doing serology tests for COVID-19, as different individuals will have different immune system responses to COVID-19 infections and vaccines.
More than two years into the COVID-19 pandemic in the United States, the CDC’s COVID Data Tracker shows the number of daily cases dropped to fewer than 50,000 as of March 4, 2022, after reaching a high of 928,125 on January 3, 2022.
Meanwhile, the seven-day death rate per 100,000 people stands at 2.78. That’s significantly above the seven-day death rate reached last July of .45, but well below the 7.21 mark recorded on January 13, 2021.
“We’re clearly entering a new phase of the pandemic,” William Morice, II, MD, PhD, Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minn., told KARE11, an NBC affiliate.
Is Herd Immunity Achievable?
According to the AP, an estimated 73% of the US population is likely to be immune to the Omicron variant due to vaccination or natural immunity from contracting the disease. That calculation was done for the media outlet by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle. The IHME anticipates immunity to Omicron could rise to 80% this month, as more people receive vaccination booster shots or become vaccinated.
“Herd immunity is an elusive concept and doesn’t apply to coronavirus,” he told the Associated Press (AP).
Milton maintains populations are moving toward “herd resistance,” rather than “herd immunity.” This will transform COVID-19 into a permanent fixture with seasonal outbreaks similar to influenza.
Epidemiologist, Ali Mokdad, PhD (above), Chief Strategy Officer for Population Health and Professor of Health Metrics Science at the University of Washington in Seattle, believes the US is now much better positioned to withstand the next wave of COVID-19 cases. “I am optimistic even if we have a surge in summer, cases will go up, but hospitalizations and deaths will not,” he told the Associated Press (AP). Mokdad worked on the IHME model that calculated the 73% Omicron-immunity figure for the AP. However, he recommends continued vigilance toward COVID-19. “We’ve reached a much better position for the coming months, but with waning immunity we shouldn’t take it for granted,” he added. And so, clinical laboratories can expect to continue to play a vital role in the fight against the spread of the SARS-CoV-2 coronavirus. (Photo copyright: University of Washington.)
Herd Immunity Varies, according to the WHO
Because antibodies that developed from vaccines—or natural immunity from a previous infection—diminish over time, waning protection means even those boosted or recently recovered from COVID-19 could be reinfected. In addition, vaccination rates vary widely around the world. Our World in Data estimates only 13.6% of people in low-income countries had received one dose of the COVID-19 vaccine as of March 7, 2022.
The World Health Organization (WHO) points out that herd immunity levels vary with different diseases. Herd immunity against measles requires about 95% of a population to be vaccinated, while the threshold for polio is about 80%.
“The proportion of the population that must be vaccinated against COVID-19 to begin inducing herd immunity is not known. This is an important area of research and will likely vary according to the community, the vaccine, the populations prioritized for vaccination, and other factors,” the WHO website states.
Living with COVID-19
Nonetheless, the US appears to be moving into a new “normal” phase of living with the disease.
In an interview with Reuters, US infectious disease expert Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases (NIAID) acknowledged a need for returning to normal living even though portions of the population—immunocompromised individuals and the unvaccinated, including children under age five who are not eligible for vaccination—remain vulnerable to more severe COVID-19.
“The fact that the world and the United States—and particularly certain parts of the United States—are just up to here with COVID, they just really need to somehow get their life back,” Fauci said. “You don’t want to be reckless and throw everything aside, but you’ve got to start inching towards that. There’s no perfect solution to this.”
Most states have lifted coronavirus-related restrictions, including masking requirements. As COVID-19 cases drop in California, Gov. Gavin Newsom put in motion a plan called SMARTER (Shots, Masks, Awareness, Readiness, Testing, Education, and Rx) that no longer responds to COVID-19 as a crisis, but instead emphasizes prevention, surveillance, and rapid response to future variant-based surges in cases.
“We have all come to understand what was not understood at the beginning of this crisis, that there’s no ending, that there’s not a moment where we declare victory,” Newsom told USA Today.
Mayo Clinic’s Morice agrees. “It can’t be out of sight, out of mind, per se, but it at least gives us hope that we can get back to some level of normalcy here over the course of the year,” he said.
Since clinical laboratories played a critical role in assay development and COVID-19 testing, medical laboratory leaders should continue monitoring COVID-19 as it moves from pandemic to endemic status due to high vaccination rates and advances in treatment options.
The COVID-19 pandemic has raised awareness among healthcare consumers as well, about the critical role laboratory medicine plays in modern medicine and healthcare. Medical laboratory leaders and pathologists would be wise to amplify this message and stress the importance of clinical laboratory testing for many diseases and healthcare conditions.
MicroRNAs in urine could prove to be promising biomarkers in clinical laboratory tests designed to diagnose brain tumors regardless of the tumor’s size or malignancy, paving the way for early detection and treatment
Researchers at Nagoya University in Japan have developed a liquid biopsy test for brain cancer screening that, they claim, can identify brain tumors in patients with 100% sensitivity and 97% specificity, regardless of the tumor’s size or malignancy. Pathologists will be interested to learn that the research team developing this technology says it is simple and inexpensive enough to make it feasible for use in mass screening for brain tumors.
Neurologists, anatomic pathologists, and histopathologists know that brain tumors are one of the most challenging cancers to diagnose. This is partly due to the invasive nature of biopsying tissue in the brain. It’s also because—until recently—clinical laboratory tests based on liquid blood or urine biopsies were in the earliest stages of study and research and are still in development.
Thus, a non-invasive urine test with this level of accuracy that achieves clinical status would be a boon for the diagnosis of brain cancer.
Researchers at Japan’s Nagoya University believe they have developed just such a liquid biopsy test. In a recent study, they showed that microRNAs (tiny molecules of nucleic acid) in urine could be a promising biomarker for diagnosing brain tumors. Their novel microRNA-based liquid biopsy correctly identified 100% of patients with brain tumors.
Atsushi Natsume, MD, PhD (above), Associate Professor at Nagoya University, led the research team that created the simple, liquid biomarker urine test for central nervous system tumors that achieved 100% sensitivity and 97% specificity, regardless of the tumor’s size or malignancy. Such a non-invasive clinical laboratory test used clinically would be a boon to brain cancer diagnosis worldwide. (Photo copyright: Nagoya University.)
Well-fitted for Mass Screenings of Brain Cancer Patients
According to the National Cancer Institute (NCI), brain and other central nervous system (CNS) cancers represent 1.3% of all new cancer cases and have a five-year survival rate of only 32.6%.
In their published study, the Nagoya University scientists wrote, “There are no accurate mass screening methods for early detection of central nervous system (CNS) tumors. Recently, liquid biopsy has received a lot of attention for less-invasive cancer screening. Unlike other cancers, CNS tumors require efforts to find biomarkers due to the blood–brain barrier, which restricts molecular exchange between the parenchyma and blood.
“Additionally, because a satisfactory way to collect urinary biomarkers is lacking, urine-based liquid biopsy has not been fully investigated despite the fact that it has some advantages compared to blood or cerebrospinal fluid-based biopsy.
“Here, we have developed a mass-producible and sterilizable nanowire-based device that can extract urinary microRNAs efficiently. … Our findings demonstrate that urinary microRNAs extracted with the nanowire device offer a well-fitted strategy for mass screening of CNS tumors.”
The Nagoya University researchers focused on microRNA in urine as a biomarker for brain tumors because “urine can be collected easily without putting a burden on the human body,” said Atsushi Natsume, MD, PhD, Associate Professor in the Department of Neurosurgery at Nagoya University and a corresponding author of the study, in a news release.
A total of 119 urine and tumor samples were collected from patients admitted to 14 hospitals in Japan with CNS cancers between March 2017 and July 2020. The researchers used 100 urine samples from people without cancer to serve as a control for their test.
To extract the microRNA from the urine and acquire gene expression profiles, the research team designed an assembly-type microfluidic nanowire device using nanowire scaffolds containing 100 million zinc oxide nanowires. According to the scientists, the device can be sterilized and mass-produced, making it suitable for medical use. The instrument can extract a significantly greater variety and quantity of microRNAs from only a milliliter of urine compared to traditional methods, such as ultracentrifugation, the news release explained.
Simple Liquid-biopsy Test Could Save Thousands of Lives Each Year
While further studies and clinical trials will be necessary to affirm the noninvasive test’s accuracy, the Nagoya University researchers believe that, with the inclusion of additional technologies, a urine-based microRNA test could become a reliable biomarker for detecting brain tumors.
“In the future, by a combination of artificial intelligence and telemedicine, people will be able to know the presence of cancer, whereas doctors will be able to know the status of cancer patients just with a small amount of their daily urine,” Natsume said in the news release.
Biomarkers found in urine or blood samples that provide clinical laboratories with a simple, non-invasive procedure for early diagnosis of brain tumors could greatly increase the five-year survival rate for thousands of patients diagnosed with brain cancer each year. Such diagnostic technologies are also appropriate for hospitals and physicians interested in advancing patient-centered care.
Decision is part of UK effort to diagnose 75% of all cancers at stage I or stage II by 2028 and demonstrates to pathologists that the technology used in liquid biopsy tests is improving at a fast pace
Pathologists and medical laboratory scientists know that when it comes to liquid biopsy tests to detect cancer, there is plenty of both hope and hype. Nevertheless, following a successful pilot study at the Christie NHS Foundation Trust in Manchester, England, which ran from 2015-2021, the UK’s National Health Service (NHS) is pushing forward with the use of liquid biopsy tests for certain cancer patients, The Guardian reported.
NHS’ decision to roll out the widespread use of liquid biopsies—a screening tool used to search for cancer cells or pieces of DNA from tumor cells in a blood sample—across the UK is a hopeful sign that ongoing improvements in this diagnostic technology are reaching a point where it may be consistently reliable when used in clinical settings.
The national program provides personalized drug therapies based on the genetic markers found in the blood tests of cancer patients who have solid tumors and are otherwise out of treatment options. The liquid biopsy creates, in essence, a match-making service for patients and clinical trials.
Liquid Biopsy Genetic Testing for Cancer Patients
“The learnings from our original ‘Target’ study in Manchester were that genetic testing needs to be done on a large scale to identify rare genetic mutations and that broader access to medicines through clinical trials being undertaken across the country rather than just one site are required,” Matthew Krebs, PhD, Clinical Senior Lecturer in Experimental Cancer Medicine at the University of Manchester, told The Guardian.
Krebs, an honorary consultant in medical oncology at the Christie NHS Foundation Trust, led the Target National pilot study.
“This study will allow thousands of cancer patients in the UK to access genetic testing via a liquid biopsy. This will enable us to identify rare genetic mutations that in some patients could mean access to life-changing experimental medicines that can provide great treatment responses, where there are otherwise limited or no other treatment options available.”
Detecting cancers at earlier stages of disease—when treatment is more likely to result in improved survival—has become a strategic cancer planning priority in the UK, theBMJ noted.
“The NHS is committed to diagnosing 75% of all cancers at stage I or II by 2028, from around 50% currently,” the BMJ wrote. “Achieving such progress in less than a decade would be highly ambitious, even without disruption caused by the COVID-19 pandemic. In this context, considerable hope has been expressed that blood tests for circulating free DNA—sometimes known as liquid biopsy—could help achieve earlier detection of cancers.”
The Guardian noted that the UK’s initiative will use a liquid biopsy test made by Swiss-healthcare giant Roche.
“We can’t guarantee that we will find a fault in the genetic code of every cancer patient we recruit, or that if we do, there will be a suitable drug trial for them,” Matthew Krebs, PhD (above), lead scientist of the NHS’ Target National pilot study, told The Guardian. “However, as we learn more about the genetics of cancer in this study, it will help doctors and scientists develop new treatments to help people in the future. Ultimately, we hope liquid biopsy testing will be adopted into routine NHS care, but we need studies such as this to show the benefit of the test on a large scale and provide the evidence that patients can benefit from being matched to targeted medicines on the basis of the blood test.” (Photo copyright: Cancer Research UK Manchester Centre.)
In her article “The Promise of Liquid Biopsies for Cancer Diagnosis,” published in the American Journal of Managed Care (AJMC) Evidence-based Oncology, serial healthcare entrepreneur and faculty lecturer at Harvard Medical School Liz Kwo, MD, detailed the optimism surrounding the “revolutionary screening tool,” including its potential for:
identifying mechanisms of resistance to therapies,
measuring remaining disease after treatment,
assessing cancer relapse or resistance to treatment, and
eliminating risk surrounding traditional biopsies.
The AJMC article estimated the liquid biopsy market will be valued at $6 billion by 2030. However, Kwo also noted that clinical adoption of liquid biopsies in the US continues to face challenges.
Welch compared the investor hype surrounding liquid biopsies to that of the now-defunct blood testing company Theranos, which lured high-profile investors to pour millions into its unproven diagnostic technology.
“Effective cancer screening requires more than early detection. It also requires that starting therapy earlier helps people live to older ages than they would if they started treatment later,” he wrote. “If that doesn’t happen, liquid biopsies will only lead to people living longer with the knowledge they have a potentially incurable disease without extending their lives. These people would be subjected to cancer therapies and their toxicities earlier, but at a time when they would otherwise be experiencing no cancer-related signs or symptoms.”
And so, while there’s much excitement about the possibility of a minimally invasive way to detect cancer, anatomic pathology groups and clinical laboratories will have to wait and see if the hype and hope surrounding liquid biopsies is substantiated by further research.
Smaller cities and rural towns are finding the NWSS a useful early warning tool for tracking COVID-19 in their communities
In a move that mirrors similar programs around the world, the federal Centers for Disease Control and Prevention (CDC) now monitors sewage nationwide and records levels of SARS-CoV-2 in an effort to prevent new outbreaks of COVID-19 and spot any new variants of the coronavirus.
Advances in gene sequencing technologies are enabling the CDC’s National Wastewater Surveillance System (NWSS), and in many communities, clinical laboratories and health system laboratories have worked with local health authorities to test wastewater since onset of the pandemic.
“What started as a grassroots effort by academic researchers and wastewater utilities has quickly become a nationwide surveillance system with more than 34,000 samples collected representing approximately 53 million Americans,” noted epidemiologist Amy Kirby, PhD (above) during the telebriefing.
Kirby is a Senior Service Fellow in the Waterborne Disease Prevention Branch at the CDC.
“Currently, CDC is supporting 37 states, four cities, and two territories to help develop wastewater surveillance systems in their communities. More than 400 testing sites around the country have already begun their wastewater surveillance efforts,” she added.
“Estimates suggests between 40% and 80% of people with COVID-19 shed viral RNA in their feces, making wastewater and sewage an important opportunity for monitoring the spread of infection,” said epidemiologist Amy Kirby, PhD (above), a Senior Service Fellow in the Waterborne Disease Prevention Branch at the CDC. The NWSS’ findings could enable public health officials to better allocate mobile clinical laboratory testing and COVID-19 vaccination sites around the country. This would be especially beneficial in rural and underserved healthcare populations. (Photo copyright: Center for Global Safe Water, Sanitation, and Hygiene.)
Genetic Sequencing Enables Tracking of Virus and Bacteria
At the time of the telebriefing, the federal agency anticipated having an additional 250 sites online within a few weeks and even more sites added within the coming months. Many of the participating sites are sequencing the genes of their biological samples and reporting that data to the CDC.
“So, we’ve seen from very early days in the pandemic that rates of detection in wastewater correlate very well with other clinical indicators, like pace rates and hospitalization and test positivity,” Kirby stated. “That data continues to come in and it continues to be a very solid indicator of what’s going on in the community.”
Wastewater, also referred to as sewage, includes water from toilets, showers, and sinks that may contain human fecal matter and water from rain and industrial sources. To use the CDC’s wastewater surveillance system:
Wastewater is collected from a community area served by the surveillance system as it flows into a local water treatment plant.
Collected samples are sent to an environmental or public health laboratory where they are tested for SARS-CoV-2.
Health departments submit the testing data to the CDC through the online NWSS Data Collection and Integration for Public Health Event Response (DCIPHER) portal.
The DCIPHER system then analyzes the data and reports the results back to the health department for use in their COVID-19 response.
Beginning in February 2022, members of the public can view the results of collected data online through the CDC’s COVID Data Tracker.
Wastewater Sampling Is a ‘Critical Early Warning System’
According to the CDC NWSS website, there are many advantages to using wastewater surveillance in the fight against COVID-19, including:
Wastewater can capture the presence of the virus shed by people both with and without symptoms.
Health officials can determine if infections are increasing or decreasing within a certain monitoring site.
Wastewater surveillance does not depend on people having access to healthcare or the availability of COVID-19 testing.
It is possible to implement wastewater surveillance in many communities as nearly 80% of the US population are served by municipal wastewater collection systems.
“These built-in advantages can inform important public health decisions, such as where to allocate mobile testing and vaccination sites,” Kirby said. “Public health agencies have also used wastewater data to forecast changes in hospital utilization, providing additional time to mobilize resources and preparation for increasing cases.”
The wastewater sampling represents a critical early warning system for COVID-19 surges and variants, and the CDC hopes this type of sampling and research can be utilized in the future for other infectious diseases.
“Wastewater surveillance can be applicable to a wide variety of health concerns. And so, we are working to expand the National Wastewater Surveillance platform to use it for gathering data on other pathogens, and we expect that work to commence by the end of this year,” Kirby said. “Our targets include antibiotic resistance, foodborne infections like E. Coli, salmonella, norovirus, influenza, and the emerging fungal pathogen Candida Auris.”
Critical Surveillance Tool for Microbiology Laboratories
Independent of the nation’s network of public health laboratories, expansion of this program may give microbiology and clinical laboratories in smaller cities and rural towns an opportunity to test wastewater specimens in support of local wastewater monitoring programs.
As the CDC develops this surveillance network into a more formal program, microbiology labs may find it useful to learn which infectious diseases are showing up in their localities, often days or weeks before any patients test positive for the same infectious agents.
That would give pathologists and clinical laboratory leaders an early warning to be on the alert for positive test results of infectious diseases that wastewater monitoring has confirmed exist in the community.
At that reduced cost, clinical laboratories in developing countries with no access to WGS could have it as a critical tool in their fight against the spread of deadly bacteria and viruses
New research into a low-cost way to sequence bacterial genomes—for as little as $10—is predicted to give public health authorities in low- and middle-income countries (LMICs) a new tool with which to more quickly identify and control disease outbreaks.
This new approach offers an alternative to more expensive Whole genome sequencing (WGS) methodologies, which clinical laboratories in developed countries typically use to identify and track outbreaks of infectious diseases. And with SARS-CoV-2 variants resulting in increased COVID-19 infections, the ability to perform low-cost, rapid, and accurate WGS is becoming increasingly important.
But for many developing countries that need it the most, the cost of WGS has kept this critical technology out of reach.
Now, a global consortium of scientists has successfully established an efficient and inexpensive pipeline for the worldwide collection and sequencing of bacterial genomes. The large-scale sequencing method could potentially provide researchers in LIMCs with tools to sequence large numbers of bacterial and viral pathogens. This discovery also could strengthen research collaborations and help tackle future pandemics.
The team of scientists, led by researchers at the Earlham Institute and the University of Liverpool, both located in the UK, are confident their technology can be made accessible to clinical laboratories in LMICs around the globe.
“It has been 26 years since the first bacterial genome was sequenced, and it is now possible to sequence bacterial isolates at scale,” Neil Hall, PhD (above), director of the Earlham Institute and one of the authors of the study, told Genetic Engineering and Biotechnology News. “However, access to this game-changing technology for scientists in low- and middle-income countries has remained restricted. The need to ‘democratize’ the field of pathogen genomic analysis prompted us to develop a new strategy to sequence thousands of bacterial isolates with collaborators based in many economically challenged countries.” (Photo copyright: Earlham Institute.)
Streamlining Collection and Sequencing
The international team of scientists aimed their innovative WGS approach at streamlining the collection and sequencing of bacterial isolates (variants). The researchers collected more than 10,400 clinical and environmental bacterial isolates from several LMICs in less than a year. They optimized their sample logistics pipeline by transporting the bacterial isolates as thermolysates from other countries to the UK. Those isolates were sequenced using a low cost, low input automated method for rapid WGS. They then performed the gene library construction and DNA sequencing analysis for a total reagent cost of less than $10 per genome.
The scientists focused their research on Salmonella enterica, a pathogen that causes infections and deadly diseases in human populations. Non-typhoidal Salmonella (NTS) have been associated with enterocolitis, a zoonotic disease in humans linked to industrial food production.
Because the disease is common in humans, there have been more genome sequences generated for Salmonella than any other type of germ.
“In recent years, new lineages of NTS serovars Typhimurium and Enteritidis have been recognized as common causes of invasive bloodstream infections (iNTS disease), responsible for about 77,000 deaths per year worldwide,” the researchers wrote in their Gen Biology paper. “Approximately 80% of deaths due to iNTS disease occurs in sub-Saharan Africa, where iNTS disease has become endemic.”
Increasing Access to Genomics Technologies in Developing Countries
The research consortium 10,000 Salmonella Genomes Project (10KSG) led the large-scale WGS initiative. The alliance involves contributors from 25 institutions in 16 countries and was designed to generate information relevant to the epidemiology, drug resistance, and virulence factors of Salmonella using WGS techniques.
“One of the most significant challenges facing public health researchers in LMICs is access to state-of-the-art technology, Jay Hinton, PhD, Professor of Microbial Pathogenesis at the University of Liverpool and one of the paper’s authors, told Technology Networks. “For a combination of logistical and economic reasons, the regions associated with the greatest burden of severe bacterial disease have not benefited from widespread availability of WGS. The 10,000 Salmonella genomes project was designed to begin to address this inequality.”
The authors noted in their study that the costs associated with sequencing have remained high mostly due to sample transportation and library construction and the fact that there are only a few centers in the world that have the ability to handle large-scale bacterial genome projects.
“Limited funding resources led us to design a genomic approach that ensured accurate sample tracking and captured comprehensive metadata for individual bacterial isolates, while keeping costs to a minimum for the Consortium,” Hall told Genetic Engineering and Biotechnology News(GEN). “The pipeline streamlined the large-scale collection and sequencing of samples from LMICs.”
“The number of publicly available sequenced Salmonella genomes reached 350,000 in 2021 and are available from several online repositories,” he added. “However, limited genome-based surveillance of Salmonella infections has been done in LMICs, and the existing dataset did not accurately represent the Salmonella pathogens that are currently causing disease across the world.”
The $10 cost is designed to help healthcare systems in developing countries identify the specific genetic composition of infectious diseases. That’s the necessary first step for developing a diagnostic test that enables physicians to make an accurate diagnosis and initiate appropriate therapy.
“The adoption of large-scale genome sequencing and analysis of bacterial pathogens will be an enormous asset to public health and surveillance in LMI countries,” molecular microbiologist Blanca Perez Sepulveda, PhD, told GEN. Sepulveda is a postdoctoral Researcher at the University of Liverpool and one of the authors of the study.
Improvement in next-generation sequencing technology has reduced costs, shortened turnaround time (TAT), and improved accuracy of whole genome sequencing. Once this low-cost method for collecting and transporting bacterial sequences becomes widely available, clinical laboratories in developing countries may be able to adopt it for genome analysis of different strains and variants of bacteria and viruses.
