At present, medical laboratories are collecting blood specimens for testing by authorized public health labs. However, clinical laboratories should prepare for the likelihood they will be called on to perform the testing using the CDC test or other tests under development.
“We need to be vigilant and understand everything related to the testing and the virus,” said Bodhraj Acharya, PhD, Manager of Chemistry and Referral Testing at the Laboratory Alliance of Central New York, in an exclusive interview with Dark Daily. “If the situation comes that you have to do the testing, you have to be ready for it.”
The current criteria for determining PUIs include clinical features, such as fever or signs of lower respiratory illness, combined with epidemiological risks, such as recent travel to China or close contact with a laboratory-confirmed COVID-19 patient. The CDC notes that “criteria are subject to change as additional information becomes available” and advises healthcare providers to consult with state or local health departments if they believe a patient meets the criteria.
Bodhraj Acharya, PhD (above), is Manager of Chemistry and Referral Testing at the Laboratory Alliance of Central New York. In an exclusive interview with Dark Daily, he stressed the importance that medical laboratories be prepared. “We need to be vigilant and be active and understand everything related to this virus and the testing. That’s the role of clinical laboratory scientists, to be ready because this can become a pandemic anytime. It can spread and tomorrow the CDC could announce it is disseminating the test to designated laboratories.” (Photo copyright: Laboratory Alliance of Central New York.)
Test Kit Problems Delay Diagnoses
On Feb. 4, the FDA issued a Novel Coronavirus Emergency Use Authorization (EUA) allowing state and city public health laboratories, as well as Department of Defense (DoD) labs, to perform presumptive qualitative testing using the Real-Time Reverse Transcriptase PCR (RT-PCR) diagnostic panel developed by the CDC. Two days later, the CDC began distributing the test kits, a CDC statement announced. Each kit could test 700 to 800 patients, the CDC said, and could provide results from respiratory specimens in four hours.
However, on Feb. 12, the agency revealed in a telebriefing that manufacturing problems with one of the reagents had caused state laboratories to get “inconclusive laboratory results” when performing the test.
“When the state receives these test kits, their procedure is to do quality control themselves in their own laboratories,” said Nancy Messonnier, MD, Director of the CDC National Center for Immunization and Respiratory Diseases (NCIRD), during the telebriefing. “Again, that is part of the normal procedures, but in doing it, some of the states identified some inconclusive laboratory results. We are working closely with them to correct the issues and as we’ve said all along, speed is important, but equally or more important in this situation is making sure that the laboratory results are correct.”
During a follow-up telebriefing on Feb. 14, Messonnier said
that the CDC “is reformulating those reagents, and we are moving quickly to get
those back out to our labs at the state and local public health labs.”
Above is a picture of CDC’s laboratory test kit for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CDC is shipping the test kits to laboratories CDC has designated as qualified, including US state and local public health laboratories, Department of Defense (DOD) laboratories, and select international laboratories. The test kits are bolstering global laboratory capacity for detecting SARS-CoV-2. (Photo and caption copyright: Centers for Disease Control and Prevention.)
Serologic Test Under Development
The current test has to be performed after a patient shows
symptoms. The “outer bound” of the virus’ incubation period is 14 days, meaning
“we expect someone who is infected to have symptoms some time during those 14
days,” Messonnier said. Testing too early could “produce a negative result,”
she continued, because “the virus hasn’t established itself sufficiently in the
system to be detected.”
Messonnier added that the agency plans to develop a serologic test that will identify people who were exposed to the virus and developed an immune response without getting sick. This will help determine how widespread it is and whether people are “seroconverting,” she said. To formulate this test, “we need to wait to draw specimens from US patients over a period of time. Once they have all of the appropriate specimens collected, I understand that it’s a matter of several weeks” before the serologic test will be ready, she concluded.
“Based on what we know now, we believe this virus spreads
mainly from person to person among close contacts, which is defined [as] about
six feet,” Messonnier said at the follow-up telebriefing. Transmission is
primarily “through respiratory droplets produced when an infected person coughs
or sneezes. People are thought to be the most contagious when they’re most
symptomatic. That’s when they’re the sickest.” However, “some spread may happen
before people show symptoms,” she said.
The virus can also spread when people touch contaminated surfaces and then touch their eyes, nose, or mouth. But it “does not last long on surfaces,” she said.
Where the Infection Began
SARS-CoV-2 was first identified during an outbreak in Wuhan, China, in December 2019. Soon thereafter, hospitals in the region “were overwhelmed” with cases of pneumonia, Dr. Acharya explained, but authorities could not trace the disease to a known pathogen. “Every time a new pathogen originates, or a current pathogen mutates into a new form, there are no molecular tests available to diagnose it,” he said.
So, genetic laboratories used next-generation sequencing, specifically unbiased nontargeted metagenomic RNA sequencing (UMERS), followed by phylogenetic analysis of nucleic acids derived from the hosts. “This approach does not require a prior knowledge of the expected pathogen,” Dr. Acharya explained. Instead, by understanding the virus’ genetic makeup, pathology laboratories could see how closely it was related to other known pathogens. They were able to identify it as a Betacoronavirus (Beta-CoVs), the family that also includes the viruses that cause SARS and Middle East Respiratory Syndrome (MERS).
This is a fast-moving story and medical laboratory leaders are advised to monitor the CDC website for continuing updates, as well as a website set up by WHO to provide technical guidance for labs.
At The Dark Report’s annual Lab Quality Confab for clinical laboratory administrators, managers, and quality team members, experts outline how disruption in healthcare requires labs to improve processes and cut costs
This is an opportunity for clinical laboratory directors,
pathologists, and other lab professionals, to comment on the proposed revisions
to CLIA before or during the upcoming CLIAC meeting on Nov. 6.
The agenda for the meeting is posted on the CDC’s website.
Public to be Heard on CLIA Regulations
“For the first time in its 26-year history, the council has
called for three workgroups to address how to revise CLIA,” Salerno said. The
workgroups will address these topics:
“It’s a dramatic step for the government to ask the
laboratory community how to revise the CLIA regulations,” Salerno commented.
Chartered in 1992, the advisory council meets twice a year, once in April and
once in November.
In the coming weeks, Dark Daily will publish more
information on how clinical laboratory professionals can comment on the
important issue of CLIA revisions.
Digital slides from Salerno’s keynote address are posted on LQC’s presentations website.
Clinical Laboratory Testing is Increasing in Value,
Keynote Speaker Says
As a service to clinical laboratories, Salerno outlined many
of the services the CDC’s Division of Laboratory Systems provides for free to
clinical labs, including information on such topics as:
During his remarks at the 13th Annual Lab Quality Confab in Atlanta, Salerno had good news for the clinical laboratory professionals in attendance. He said that lab testing was becoming a more valued commodity in healthcare because physicians and other providers were growing increasingly confident in lab test results. [Photo copyright: The Dark Report.]
Healthcare System Disruption Impacts Providers, Including
Clinical Laboratories
Other keynote speakers addressed how disruption in the US
healthcare systems affects provider organizations in significant ways. For
clinical laboratories, such disruption has resulted in reduced payment and
demands for quality improvement and shorter turnaround times.
For all these reasons, quality
management systems may be every clinical laboratory’s best strategy to
survive and thrive, the keynote speakers said.
The first keynoter was Robert L. Michel, Editor-in-Chief and Publisher of The Dark Report. Michel’s remarks focused on how price cuts from Medicare, Medicaid, private payers, and the drive for value-based payment, are requiring labs to do more with less. For this reason, quality management systems are necessary for all labs seeking to improve results, eliminate errors, and cut costs, he said.
“The people closest to the work know how to fix these
problems,” he added. “That’s why labs know they must train their staff to
identify problems and then report them up the chain so they can be fixed,”
Michel commented. “Labs that are best at listening to their employees are
getting very good at identifying problems by measuring results and monitoring
and reporting on their own performance.”
Michel identified three principle factors that are
disrupting healthcare:
The shift from reactive care in which the health system cares for sick patients to proactive care in which the health system aims to keep patients healthy and out of the hospital and other costly sites of care.
The transition away from fee-for-service payment that encourages providers to do more for patients, whether more care is needed or not, to value-based payment that aims to reward providers for keeping patients healthy.
The consolidation among hospitals, health systems, physicians, and other providers. A trend that requires clinical laboratories to find new partners and new ways to improve lab services and reduce costs.
Informatics Performance Data Help Clinical Laboratories
Respond to Change
“The attributes of new and successful labs are that they will have faster workflow and shorter cycle times for clinical lab tests and anatomic pathology specimen results,” Michel explained. “That means that labs will attack non-value-added processes by implementing continuous improvement strategies [such as Lean and Six Sigma] and by the sophisticated use of informatics.”
Making use of performance data enables clinical laboratory
directors to make changes in response to disruptions that affect healthcare.
“If you have good informatics, then seven or eight of every 10 decisions you
make will be good decisions, and with the other two and three decisions, you’ll
have time to pull back and adjust,” Michel commented.
The second keynote speaker, Jeremy Schubert, MBA, MPH, Division Vice President of Abbott, reiterated what Michel said about how the health system is moving away from fee-for-service payment. Instead of focusing on caring for sick patients exclusively, he said, health insurers are paying all healthcare providers to keep patients healthy.
“Healthcare today is about the whole life course of the
individual,” Schubert explained. “Patients no longer want healthcare only when
they’re sick. Instead, they want to be healthy. And health creation is not just
about a person’s physical health. It’s about their mental health, their
emotional health, and their social wellbeing.
“In fact,” he continued, “you can learn more about a
person’s health from their Zip code than from their genetic code.”
That is essentially what TriCore Reference Laboratories (TriCore) has been doing in New Mexico, Schubert added. During his presentation, Michel mentioned TriCore as being one of four clinical laboratories participating in Project Santa Fe, a non-profit organization that promotes the movement from Clinical Lab 1.0 to Clinical Lab 2.0. (See “TriCore Forges Ahead to Help Payers Manage Population Health,” The Dark Report, May 20, 2019.)
“If you want to be a quality engine in healthcare you have
to be operating at Lab 2.0. Who is best qualified to interpret information?
It’s the lab,” Schubert said. Then he challenged labs to begin pursuing the
goal of achieving Lab 3.0, saying “Lab 3.0 is being able to interface with the
patient to address each patient’s problems.”
The 13th Annual Lab Quality Confab (LQC) in Atlanta continues through the 17th with post-event workshops in Six Sigma and mastering quality management systems. In attendance are 300 clinical laboratory administrators, managers, and quality team members who are learning a complete array of professional training methods.
To register to attend, click here or enter https://www.labqualityconfab.com/register into your browser, or call 707-829-9485, or e-mail lqcreg@amcnetwork.com.
Using animal blood, the researchers hope to improve the accuracy of AI driven diagnostic technology
What does a cheetah, a tortoise, and a Humboldt penguin have
in common? They are zoo animals helping scientists at Saarland University in
Saarbrücken, Germany, find biomarkers that can help computer-assisted diagnoses
of diseases in humans at early stages. And they are not the only animals
lending a paw or claw.
In their initial research, the scientists used blood samples
that had been collected during routine examinations of 21 zoo animals between
2016 and 2018, said a news
release. The team of bioinformatics
and human genetics experts
worked with German zoos Saarbrücken and Neunkircher for the study. The project
progresses, and thus far, they’ve studied the blood of 40 zoo animals, the
release states.
This research work may eventually add useful biomarkers and
assays that clinical
laboratories can use to support physicians as they diagnose patients,
select appropriate therapies, and monitor the progress of their patients. As medical
laboratory scientists know, for many decades, the animal kingdom has been
the source of useful insights and biological materials that have been
incorporated into laboratory assays.
“Measuring the molecular blood profiles of animals has never
been done before this way,” said Andreas
Keller, PhD, Saarland University Bioinformatics Professor and Chair for
Clinical Bioinformatics, in the news release. The Saarland researchers published
their findings in Nucleic Acids
Research, an Oxford
Academic journal.
“Studies on sncRNAs [small non-coding RNAs] are often largely based on homology-based information, relying on genomic sequence similarity and excluding actual expression data. To obtain information on sncRNA expression (including miRNAs, snoRNAs, YRNAs and tRNAs), we performed low-input-volume next-generation sequencing of 500 pg of RNA from 21 animals at two German zoological gardens,” the article states.
Can Animals Improve the Accuracy of AI to Detect Disease
in Humans?
However, the researchers perceived an inability for AI and machine learning to
discern real biomarker patterns from those that just seemed to fit.
“The machine learning methods recognize the typical
patterns, for example for a lung tumor or Alzheimer’s disease. However, it is
difficult for artificial intelligence to learn which biomarker patterns are
real and which only seem to fit the respective clinical picture. This is where
the blood samples of the animals come into play,” Keller states in the news
release.
“If a biomarker is evolutionarily conserved, i.e. also
occurs in other species in similar form and function, it is much more likely
that it is a resilient biomarker,” Keller explained. “The new findings are now
being incorporated into our computer models and will help us to identify the
correct biomarkers even more precisely in the future.”
Andreas Keller, PhD (left), and zoo director Richard Francke (right), hold a pair of radiated tortoises that participated in the Saarland University study. (Photo copyright: Oliver Dietze/Saarland University.)
“Because blood can be obtained in a standardized manner and
miRNA expression patterns are technically very stable, it is easy to accurately
compare expression between different animal species. In particular, dried blood
spots or microsampling devices appear to be well suited as containers for
miRNAs,” the researchers wrote in Nucleic Acids Research.
Animal species that participated in the study include:
Additionally, human volunteers contributed blood specimens
for a total of 19 species studied. The scientists reported success in capturing
data from all of the species. They are integrating the information into their
computer models and have developed a public database of their
findings for future research.
“With our study, we provide a large collection of small RNA
NGS expression data of species that have not been analyzed before in great
detail. We created a comprehensive publicly available online resource for
researchers in the field to facilitate the assessment of evolutionarily
conserved small RNA sequences,” the researchers wrote in their paper.
Clinical Laboratory Research and Zoos: A Future
Partnership?
This novel involvement of zoo animals in research aimed at improving
the ability of AI driven diagnostics to isolate and identify human disease is
notable and worth watching. It is obviously pioneering work and needs much
additional research. At the same time, these findings give evidence that there
is useful information to be extracted from a wide range of unlikely sources—in
this case, zoo animals.
Also, the use of artificial intelligence to search for
useful patterns in the data is a notable part of what these researchers
discovered. It is also notable that this research is focused on sequencing DNA
and RNA of the animals involved with the goal of identifying sequences that are
common across several species, thus demonstrating the common, important
functions they serve.
In coming years, those clinical laboratories doing genetic
testing in support of patient care may be incorporating some of this research
group’s findings into their interpretation of certain gene sequences.
Cloud-based platform—IDseq—shows potential to track the causes and spread of infectious diseases worldwide using metagenomic data
Here’s the latest example of how big data and related technologies can give physicians—as well as microbiologists and clinical pathologists—a new tool for understanding infectious disease and tracking outbreaks anywhere in the world. This project is being funded and organized by well-known Silicon Valley entrepreneurs.
The project is known as IDseq. It was announced recently in a press release issued by Chan Zuckerberg Biohub (CZ Biohub), Chan Zuckerberg Initiative (CZI), and the Bill and Melinda Gates Foundation. IDseq is a platform designed to support global disease surveillance and prevention. It will make use of gene sequencing and analysis of metagenomic data. This data will be made accessible to the global medical community.
The system leverages the power of cloud computing to streamline the process of transmitting and analyzing metagenomic data, as well as sharing results with other platform users.
“That will be incredibly valuable. Information sharing is one of the most powerful public-health interventions in an outbreak,” Jennifer Gardy, PhD, an epidemiologist at the University of British Columbia, told The Atlantic.Designed by Engineers to Be Easily Used by Healthcare Providers and Medical Laboratory Technicians
Coverage in The Atlantic notes that IDseq isn’t the first tool to offer similar features. Joseph DeRisi, PhD, a biochemist at the University of California San Francisco and co-president of CZ Biohub, states, however, that IDseq is one of the first designed by a large team of engineers, security experts, and other tech and medical researchers.
Many tools see their origins in academic research and are less friendly to those without advanced academic expertise. The research team’s goal, according to DeRisi, is for IDseq “To enable people in under-resourced areas to do what we’ve been trying to do in San Francisco.”
“It’s easy for us to sit in our labs dreaming up tools and platforms,” Jennifer Gardy, PhD (above), an epidemiologist at the University of British Columbia, told The Atlantic. “But we need to make sure we’re designing them in a way that makes sense to the doctors, nurses, lab techs, and epidemiologists out there in an outbreak.” (Photo copyright: Michelle Thorpe/University of British Columbia.)
Two Trials Show Promise for IDseq Use
While the software is already available for free as a collection of open source tools, the IDseq platform is now in a “soft launch” phase. The Bill and Melinda Gates Foundation is funding training for clinicians at CZ Biohub’s labs in San Francisco through its Grand Challenges Explorations Initiative.
However, the platform has already achieved success in two noted scenarios—one at Dhaka Shishu Hospital in Dhaka, Bangladesh, and another in Tororo District Hospital in Uganda. Both used the system to analyze the samples of children admitted for fevers for which they found no known cause.
In the Dhaka cases, Senjuti Saha, PhD, a microbiologist from Child Health Research Foundation, used the platform to trace unexplained cases of meningitis to an earlier chikungunya virus outbreak. Saha explained to The Atlantic that her colleagues previously thought chikungunya could not cause meningitis. The platform found otherwise, allowing her to analyze a further 478 samples and detect an additional 17 cases of potential chikungunya-related meningitis.
In the Uganda cases, the researchers used metagenomic next-generation sequencing (mNGS) data and the IDseq platform to investigate unknown causes of fever in children.
“As progress is made toward elimination of malaria in sub-Saharan Africa, it will be increasingly important to understand the landscape of pathogens that account for the remaining burden of morbidity and mortality,” researchers state in their study, currently in early access at bioRxiv. “The use of mNGS can contribute importantly to this understanding, offering unbiased identification of infecting pathogens.”
Wide-Spread Use of IDseq Not Without Challenges
While an article in Medium by Charles de Bourcy, PhD, Software Engineer at Chan Zuckerberg Initiative, outlines how the IDseq platform can process up to 480GB in approximately 10 minutes, it doesn’t account for the initial data input, which can be daunting.
For areas with weak infrastructure and/or slow connection speeds, this could add significant delays as medical laboratories and healthcare workers at remote sites attempt to transfer data to the nearest IDseq-enabled location. Saha told The Atlantic, “If the transfer is too slow or the data too large, we just [ship] hard drives.”
Sequencing requirements create additional concerns. Bulky equipment and the skills required to run sequencers could limit the ability to use the IDseq platform to analyze and share results. Clinicians might also face difficulties in sourcing sequencing reagents due to customs and supply chain concerns.
Finally, the platform still requires an expert to interpret findings. “IDseq is an excellent tool, but it needs to be paired with people who have substantive knowledge to guide its use,” Saha told The Atlantic.
Regardless of these issues, Saha believes IDseq can help remote/resource-challenged medical labs chase diseases. “It doesn’t solve all the problems, but it means that groups like ours don’t have to spend time to build up [sequencing] capacity. And anything is better than nothing.”
IDseq might offer an excellent opportunity for microbiology laboratories, clinical laboratories, and medical researchers around the world to share data surrounding outbreaks, track disease on global and community level, and better determine the strains and probable sources of infectious diseases.
As personalized medicine becomes more popular, clinical laboratories, and anatomicpathologists are uniquely positioned to use next-generation sequencing to advance their scope among regulators, insurers, providers and patients, while adding clinical value and generating a new revenue source
By now, most clinical pathologists and medical laboratory scientists recognize that genetics, genetic testing, and gene sequencing will be a major transformative force in this country’s healthcare system. Genetics is the future of modern medicine.
At the same time, most independent labs and health network labs still lack the key resources needed for them to provide accurate and state-of-the-art genetic testing and gene sequencing services in support of clinical care.
The good news is that it is not yet prime time for genetic testing—meaning few genetic tests have become part of routine care, particularly in primary care settings. Today’s limited use of genetic tests creates the opportunity for any medical laboratory and anatomic pathology group to use this time to develop its genetic testing strategy. It also has time to incrementally put in place the resources it will need to offer genetic testing and gene sequencing services to its client physicians.
“Every clinical lab that wants to be a provider of genetic tests needs three basic resources,” stated Robert L. Michel, Editor-in-Chief of The Dark Report and Dark Daily. “First, the lab must have information technology in place that can handle genetic and molecular data. The second thing needed are pathologists, PhDs, and clinical laboratory scientists trained in genetic and molecular diagnostics. Of course, the third resource is to have the lab analyzers, instruments, and automation needed to extract, amplify, and sequence specimens.”
Experts agree that adoption of genetic testing will happen at a rapid pace. “Next-generation sequencing (NGS) is an incredibly powerful, positive force in medical care. We were in the Dark Ages before this. It is the tsunami on our shores, and it’s going to take over all of medicine. It’s not a trend. It’s the future of medicine. There’s no question about it,” predicts Maurie Markman, MD, an oncologist and President of Medicine and Science at Cancer Treatment Centers of America, in an article he penned for Health Connect South.
“As knowledge of genomic medicine has increased, its cost has plummeted,” notes Maurie Markman, MD (above), President of the Cancer Treatment Centers of America, in his Health Connect South article. “Sequencing a human genome [in 2015] costs less than $10,000, compared to more than $100 million in 2001. Not only are the tests more available to patients, but more oncologists are trying their hand at tumor testing and building on the base of knowledge.” (Photo copyright: Cancer Treatment Centers of America.)
“If you agree with Markman’s comments, then your medical lab should have a plan for how it will incorporate NGS technologies and genetic testing into its menu of lab tests,” observed Michel. “Because NGS is the engine powering much of this new genetic information and igniting the potential of personalized medicine, probably the single most important business step clinical labs and pathology groups can take at this point is to begin to create the informatics capabilities needed to support genetic testing.
“This can be done by either adding the needed functions to the existing laboratory information system (LIS) or supplementing that LIS with appropriate middleware solutions,” he continued. “This is true even if a lab plans to outsource both the gene sequencing and the annotation and interpretation of the resulting gene sequences. It will need in-house informatics capabilities to store and report that genetic information.”
NGS, Gene Sequencing, Precision Medicine, and Clinical Laboratories
Purchasing, implementing, and operating NGS technologies can be a costly venture, so it is critical that labs know and understand the needs of their referring clients.
“Knowing who your lab’s customers are and what you do for them today should guide you as a laboratory,” notes Brian Keefe, Vice President of Sales and Customer Innovation at Psyche Systems, a laboratory solutions developer for the medical industry based in Boston. “For example, your pathology group knows it should be offering NGS testing, and the justification for needing to go in this direction is because 90% of your clients are oncologists.”
Using NGS technology and marketing it to clients will be a valuable benefit for clinical laboratories. It will enable labs to participate in personalized medicine and allow them to become the “go to” facility for specific genetic tests.
“If you’re a laboratory that has figured out how to map the genome for nightmare bacteria, it doesn’t matter whether you’re three miles or 3,000 miles away, physicians will send their samples to your lab regardless of the distance,” Keefe notes. “If your lab is first to market, you establish powerful brand recognition and attract positive attention, which justifies your lab’s cost to set up and offer that testing in the first place.”
Learn More by Requesting the Dark Daily NGS White Paper
To help medical laboratories and anatomic pathology groups learn more about the growing role of NGS in clinical care, and how NGS can benefit clinical and molecular laboratories, Dark Daily and The Dark Report have produced a white paper titled, “How Next-Generation Sequencing Helps Molecular Laboratories Deliver Personalized Medicine Services to their Client Physicians.”
Medical laboratory leaders who want to learn how labs can establish NGS services and implement the IT/Informatics needed to be successful in using NGS should request a copy of this important white paper. It reviews how pathologists can help providers select targeted therapies and touches on marketing strategies to use NGS to procure new customers and retain existing customers.
The NGS white paper can be downloaded at no cost by clicking here or placing https://www.darkdaily.com/how-next-generation-sequencing-helps-molecular-laboratories-deliver-personalized-medicine-services-to-their-client-physicians-601/ into your browser.
