Though some experts claim widespread antibody testing is key to effective public health safety, the WHO warns positive serological tests may not indicate immunity from reinfection or transmission of SARS-CoV-2
It may be the largest program of clinical laboratory testing ever conducted in the United States. Health officials are preparing to undertake large-scale serological surveys (serosurveys) to detect and track previously undetected cases of SARS-CoV-2, the novel coronavirus, that causes the COVID-19 illness.
Microbiologists, epidemiologists, and medical laboratory leaders will be interested in these studies, which are aimed at determining how many adults in the US with no confirmed history of SARS-CoV-2 infection actually possess antibodies to the coronavirus.
Serological screening testing may also enable employers to identify employees who can safely return to their job. And researchers may be able to identify communities and populations that have been most affected by the virus.
Serological Study of COVID-19 Taking Place in Five States
In an interview with Science, Michael Busch, MD, PhD, Senior Vice President, Research and Scientific Affairs of Vitalant (formerly Blood Systems), one of the nation’s oldest and largest nonprofit community blood service providers, and Director of the Vitalant Research Institute, discussed several serological studies in which he is involved. The first study, which he said is being funded by the National Institutes of Health (NIH), is taking place in six metropolitan regions in the US: Seattle, New York City, San Francisco, Los Angeles, Boston, and Minneapolis.
The interesting twist in these studies is that they will test blood samples from people donating blood. In March, participating blood centers in each region started saving 1,000 donor samples per month. Six thousand samples will be assessed monthly for a six-month period using an antibody testing algorithm that enables researchers to monitor how people develop SARS-CoV-2 antibodies over time.
Busch told Science this regional study will evolve into three “national, fully representative serosurveys of the US population using blood donors.” This particular national serosurvey will study 50,000 donations in September and December of 2020 and in November 2021.
“We’re going to be estimating overall antibody prevalence to SARS-CoV-2 within each state, but also map it down within the states to regions and metropolitan urban areas, and look at the differences,” Busch told Science, which called the serosurvey “unprecedented.”
“It’s certainly the largest serosurvey I’ve ever been involved with,” Busch said.
In the third NIH serosurvey, according to Busch, NIH blood-donor serosurveys will be compared with results from population serosurveys taking place through the University of Washington and University of California San Francisco, which involve neighborhood door knocking and sampling from hematology labs.
“An antibody test is looking back into the immune system’s history with a rearview mirror,” said Matthew J. Memoli, MD (above,) an infection disease specialist with the NIH and Director of the National Institute of Allergy and Infectious Diseases (NIAID), in a news release. “By analyzing an individual’s blood, we can determine if that person has encountered SARS-CoV-2 previously.” (Photo copyright: National Institutes of Health.)
Some of the SARS-CoV-2 serological surveys underway include:
The National Institutes of Health serosurvey involving as many as 10,000 adults in the US who have no confirmed history of infection with SARS-CoV-2, which will analyze blood samples for two types of antibodies—anti-SARS-CoV-2 protein IgG and IgM. Researchers also may perform additional tests to evaluate volunteers’ immune responses to the virus.
A World Health Organization (WHO) coordinated follow-up study to its Solidarity Trial named Solidarity 2, which will “pool data from research groups in different countries to compare rates of infection,” which WHO officials say is ‘critical’ to understanding the true extent of the pandemic and to inform policy, Research Professionals News reported.
In Germany, the Robert Koch Institute, the country’s disease control and prevention agency, is tackling Europe’s first large-scale COVID-19 antibody testing. Its three-phase study will include serological testing on blood from donation centers, followed by testing on blood samples from coronavirus regional hotspots and then the country’s broader population.
But Can Serological Testing Prove Immunity to COVID-19?
However, whether having COVID-19 antibodies will make people immune to reinfection or unable to spread the disease is not yet known.
“We don’t have nearly the immunological or biological data at this point to say that if someone has a strong enough immune response that they are protected from symptoms, … that they cannot be transmitters,” Michael Mina, MD, PhD, Assistant Professor of Epidemiology at Harvard’s T.H. Chan School of Public Health and Associate Medical Director in Clinical Microbiology (molecular diagnostics) in the Department of Pathology at Brigham and Women’s Hospital, told STAT.
The Times of Sweden reported the WHO warned in mid-April that there is no proof recovering from COVID-19 provides immunity.
“There are a lot of countries that are suggesting using rapid diagnostic serological tests to be able to capture what they think will be a measure of immunity,” said Maria Van Kerkhove, PhD, the WHO’s Technical Lead for COVID-19, at a news conference in Geneva, Switzerland, the Times of Sweden reported.
“Right now, we have no evidence that the use of a serological test can show that an individual has immunity or is protected from reinfection,” she said, adding, “These antibody tests will be able to measure that level of seroprevalence—that level of antibodies—but that does not mean that somebody with antibodies [is] immune.”
In addition, the reliability and quality of some serological tests produced in China, as well as some being manufactured in the US, have come into question, the Financial Times reported.
Nevertheless, as serological testing for COVID-19 becomes more widespread, clinical laboratories should plan to play an ever-increasing role in the battle to stop a second wave of the epidemic in this country.
By offering DTC preventative gene sequencing, hospital leaders
hope to help physicians better predict cancer risk and provide more accurate
diagnoses
Two Boston health systems, Brigham and Women’s Hospital and Massachusetts General Hospital (MGH), are the latest to open preventative gene sequencing clinics and compete with consumer gene sequencing companies, such as 23andMe and Ancestry, as well as with other hospital systems that already provide similar services.
This may provide opportunities for clinical laboratories. However, some experts are concerned that genetic sequencing may not be equally available to patients of all socioeconomic classes. Nor is it clear how health systems plan to pay for the equipment and services, since health insurance companies continue to deny coverage for “elective” gene sequencing, or when there is not a “clear medical reason for it, such as for people with a long family history of cancer,” notes STAT.
Therefore, not everyone is convinced of the value of gene sequencing to either patients or hospitals, even though advocates tout gene sequencing as a key element of precision medicine.
Is Preventative Genetic Sequencing Ready for the Masses?
Brigham’s Preventive Genomics Clinic offers comprehensive DNA sequencing, interpretation, and risk reporting to both adults and children. And MGH “plans to launch its own clinic for adults that will offer elective sequencing at a similar price range as the Brigham,” STAT reported.
The Brigham and MGH already offer similar gene sequencing services as other large health systems, such as Mayo Clinic and University of California San Francisco (UCSF), which are primarily used for research and cancer diagnoses and range in price depending on the depth of the scan, interpretation of the results, and storage options.
However, some experts question whether offering the
technology to consumers for preventative purposes will benefit anyone other
than a small percentage of patients.
“It’s clearly not been demonstrated to be cost-effective to promote this on a societal basis,” Robert Green, MD, MPH, medical geneticist at Brigham and Women’s Hospital, and professor of genetics at Harvard, told STAT. “The question that’s hard to answer is whether there are long-term benefits that justify those healthcare costs—whether the sequencing itself, the physician visit, and any downstream testing that’s stimulated will be justified by the situations where you can find and prevent disease.”
Additionally, large medical centers typically charge more
for genomic scans than consumer companies such as 23andMe and Ancestry. Hospital-based
sequencing may be out of the reach of many consumers, and this concerns some
experts.
“The idea that genomic sequencing is only going to be
accessible by wealthy, well-educated patrons who can pay out of pocket is
anathema to the goals of the publicly funded Human Genome Project,” Jonathan
Berg, MD, PhD, Genetics Professor, University of North Carolina at Chapel
Hill, told Scientific
American.
And, according to the American Journal of Managed Care, “It’s estimated that by 2021, 100 million people will have used a direct-to-consumer (DTC) genetic test. As these tests continue to gain popularity, there is a need for educating consumers on their DTC testing results and validating these results with confirmatory testing in a medical-grade laboratory.”
This is why it’s critical that clinical laboratories and
anatomic pathology groups have a genetic testing and gene sequencing strategy,
as Dark
Daily reported.
David Bick, MD, Chief Medical Officer at the HudsonAlpha Institute for Biotechnology and Medical Director of the Smith Family Clinic for Genomic Medicine, told Scientific American, “there’s just more and more interest from patients and families not only because of 23andMe and the like, but because there’s just this understanding that if you can find out information about your health before you become sick, then really our opportunity as physicians to do something to help you is much greater.”
In an article he penned for Medium, Robert Green, MD, MPH (shown above counseling a patient), medical geneticist at Brigham and Women’s Hospital and professor of genetics at Harvard, wrote, “The ultimate aim of our Genomes2People Research Program is to contribute to the transformation of medicine from reactive to proactive, from treatment-oriented to preventive. We are trying to help build the evidence base that will justify societal decision to make these technologies and services accessible to anyone who wants them, regardless of means, education or race and ethnicity.” (Photo copyright: Wall Street Journal.)
Is Preventative Genomics Elitist?
As large medical centers penetrate the consumer genetic
testing market some experts express concerns. In a paper he wrote for Medium,
titled, “Is Preventive Genomics Elitist?” Green asked, “Is a service like this
further widening the inequities in our healthcare system?”
Green reported that while building the Preventive Genomics Clinic at Brigham, “we … struggled with the reality that there is no health insurance coverage for preventive genomic testing, and our patients must therefore pay out of pocket. This is a troubling feature for a clinic at Brigham and Women’s Hospital, which is known for its ties to communities in Boston with diverse ethnic and socioeconomic backgrounds.”
Most of Brigham’s early genetics patients would likely be “well-off,
well-educated, and largely white,” Green wrote. “This represents the profile of
typical early adopters in genetic medicine, and in technology writ large. It
does not, however, represent the Clinic’s ultimate target audience.”
More Data for Clinical Laboratories
Nevertheless, preventive genomics programs offered by large
health systems will likely grow as primary care doctors and others see evidence
of value.
Therefore, medical laboratories that process genetic
sequencing data may soon be working with growing data sets as more people reach
out to healthcare systems for comprehensive DNA sequencing and reporting.
Genomic analysis of pipes and sewers leading from the National Institutes of Health Clinical Care Center in Bethesda, Md., reveals the presence of carbapenem-resistant organisms; raises concern about the presence of multi-drug-resistant bacteria previously undetected in hospital settings
If hospitals and medical laboratories are battlegrounds, then microbiologists and clinical laboratory professionals are frontline soldiers in the ongoing fight against hospital-acquired infections (HAIs) and antibiotic resistance. These warriors, armed with advanced testing and diagnostic skills, bring expertise to antimicrobial stewardship programs that help block the spread of infectious disease. In this war, however, microbiologists and medical laboratory scientists (AKA, medical technologists) also often discover and identify new and potential strains of antibiotic resistance.
Potential Source of Superbugs and Hospital-Acquired Infections
According to the mBio study, “Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections.”
Karen Frank, MD, PhD (above), is Chief of the Microbiology Service Department at the National Institutes of Health and past-president of the Academy of Clinical Laboratory Physicians and Scientists. She suggests hospitals begin tracking the spread of the bacteria. “In the big picture, the concern is the spread of these resistant organisms worldwide, and some regions of the world are not tracking the spread of the hospital isolates.” (Photo copyright: National Institutes of Health.)
Frank’s team used Illumina’s MiSeq next-generation sequencer and single-molecule real-time (SMRT) sequencing paired with genome libraries, genomics viewers, and software to analyze the genomic DNA of more than 700 samples from the plumbing and sewers. They discovered a “potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes, and increase the risk of antibiotic resistant ‘superbugs’ and difficult to treat hospital-acquired infections (HAIs).”
Genomic Sequencing Identifies Silent Threat Lurking in Sewers
Frank’s study was motivated by a 2011 outbreak of antibiotic-resistant Klebsiella pneumoniae bacteria that spread through the NIHCC via plumbing in ICU, ultimately resulting in the deaths of 11 patients. Although the hospital, like many others, had dedicated teams working to reduce environmental spread of infectious materials, overlooked sinks and pipes were eventually determined to be a disease vector.
In an NBC News report on Frank’s study, Amy Mathers, MD, Director of The Sink Lab at the University of Virginia, noted that sinks are often a locus of infection. In a study published in Applied and Environmental Microbiology, another journal of the ASM, Mathers noted that bacteria in drains form a difficult to clean biofilm that spreads to neighboring sinks through pipes. Mathers told NBC News that despite cleaning, “bacteria stayed adherent to the wall of the pipe” and even “splashed out” into the rooms with sink use.
During the 2011-2012 outbreak, David Henderson, MD, Deputy Director for Clinical Care at the NIHCC, told the LA Times of the increased need for surveillance, and predicted that clinical laboratory methods like genome sequencing “will become a critical tool for epidemiology in the future.”
Frank’s research fulfilled Henderson’s prediction and proved the importance of genomic sequencing and analysis in tracking new potential sources of infection. Frank’s team used the latest tools in genomic sequencing to identify and profile microbes found in locations ranging from internal plumbing and floor drains to sink traps and even external manhole covers outside the hospital proper. It is through that analysis that they identified the vast collection of CPOs thriving in hospital wastewater.
In an article, GenomeWeb quoted Frank’s study, noting that “Over two dozen carbapenemase gene-containing plasmids were identified in the samples considered” and CPOs turned up in nearly all 700 surveillance samples, including “all seven of the wastewater samples taken from the hospital’s intensive care unit pipes.” Although the hospital environment, including “high-touch surfaces,” remained free of similar CPOs, Frank’s team noted potential associations between patient and environmental isolates. GenomeWeb noted Frank’s findings that CPO levels were in “contrast to the low positivity rate in both the patient population and the patient-accessible environment” at NIHCC, but still held the potential for transmission to vulnerable patients.
Since carbapenems are a “last resort” antibiotic for bacteria resistant to other antibiotics, the NIHCC “reservoir” of CPOs is a frightening discovery for physicians, clinical laboratory professionals, and the patients they serve.
The high CPO environment in NIHCC wastewater has the capability to spread resistance to bacteria even without the formal introduction of antibiotics. In an interview with Healthcare Finance News, Frank indicated that lateral gene transfer via plasmids was not only possible, but likely.
“The bacteria fight with each other and plasmids can carry genes that help them survive. As part of a complex bacterial community, they can transfer the plasmids carrying resistance genes to each other,” she noted. “That lateral gene transfer means bacteria can gain resistance, even without exposure to the antibiotics.”
The discovery of this new potential “reservoir” of CPOs may mean new focused genomic work for microbiologists and clinical laboratories. The knowledge gained by the discovery of CPOs in hospital waste water and sinks offers a new target for study and research that, as Frank concludes, will “benefit healthcare facilities worldwide” and “broaden our understanding of antimicrobial resistance genes in multi-drug resistant (MDR) bacteria in the environment and hospital settings.”
Public health agencies and physicians would gain access to accurate, rapid dip-stick test that could give results similar to a pregnancy test
Tuberculosis is a major killer that ranks alongside HIV/AIDS as a leading cause of death worldwide. This deadly disease takes the lives of more than a million people each year. And, unfortunately, traditional medical laboratory testing using X-rays, blood/skin/sputum specimens, or the new molecular diagnostic systems can be time consuming and expensive.
Now, scientists at George Mason University (GMU) in Virginia have developed a urine test for tuberculosis (TB) that could lead to a dip-stick technology that would accurately and rapidly diagnose the deadly lung disease. Similar to a pregnancy test, if successfully developed for use in clinical settings, the dip-stick could not only enable public health agencies to test for TB more effectively, but also allow primary care physicians and other doctors to easily test their patients for TB at the point of care. However, it also could mean clinical laboratories might find their participation.
Nearly All TB Deaths Occur in Resource Strapped Areas
Such a breakthrough would certainly be a boon to public health and global healthcare, especially in resource strapped areas of the world. According to the World Health Organization (WHO), more than 95% of the 1.7 million TB deaths each year occur in low- and middle-income countries. This is one reason why an inexpensive and easy-to-use detection method for diagnosing the lung disease has long been sought. TB is curable, particularly if diagnosed early.
George Mason University scientists Alessandra Luchini, PhD (above left), and Lance Liotta, MD, PhD (above right), head an international team that has developed a nanotechnology that may lead to a simple dipstick urine test to detect tuberculosis. Such a test could greatly impact medical laboratories by reducing the need for traditional lab tests. (Photo copyrights: George Mason University.)
While past attempts at developing an accurate urine test for TB failed to reliably detect low concentrations of the sugar entity lipoarabinomannan (LAM) in HIV-negative, TB-infected patients, the GMU team developed a technology capable of doing so.
According to New Scientist, the GMU team’s test “uses tiny molecular cages embedded with a special dye that can catch and trap these sugar molecules. This makes the test capable of detecting the sugar at low concentrations, making the technique as much as 1,000 times more accurate [than] previous methods for detecting TB in urine.”
“We can measure now what could never be measured before,” Liotta noted in a news release.
World Health Organization Recommends Not Using Serodiagnostic Blood Tests
Common methods to detect TB currently include microscopy of sputum samples—a fast and accurate but expensive detection method (that also can diagnosis drug resistant disease)—or a skin test. A third test for TB, an Interferon-Gamma Release Assay, provides results in less than 24 hours but cannot distinguish between active and latent infection. In 2011, the WHO issued a Policy Recommendation urging countries to stop using serodiagnostic blood tests to diagnose TB, calling these tests unreliable and inaccurate. X-rays, meanwhile, detect only advanced lung damage.
In the GMU study, 48 Peruvian patients were chosen, all with active pulmonary TB, none of whom was infected with HIV or previously had received treatment for TB. According to the research, TB infections were detected with greater than 95% sensitivity, with TB-positive, HIV-negative patients having detectably higher concentrations of LAM in their urine compared to the controls. Patients who had more advanced disease also had elevated LAM concentrations. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM.
“The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes … This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients,” the study’s authors told Science.
While The Scientist reports the GMU urine test gives results in about 12 hours, Luchini’s goal is for that timeframe to be dramatically shortened as the test is refined.
“We showed that our technology could be used to measure several different kinds of markers for TB in the urine and could be configured as a rapid test similar to a pregnancy test,” Luchini said in a GMU news release.
According to the university, GMU researchers will continue their work in Peru, where students will begin testing hundreds of patients as part of a research study. Grants from the National Institutes of Health and the Bill and Melinda Gates Foundation are funding their work. Luchini told New Scientist her goal is to make their TB urine test easier to use and to test it on thousands more people.
If successful, she predicts the test could be commercially available for physicians and clinical laboratories to use within three years. GMU’s biotechnology partner Ceres Nanosciences will be commercializing the technology, with the aim of making the test available worldwide, the university said in a statement.
Pathologists and clinical lab managers can help physicians more effectively select appropriate genetic tests and better interpret results to identify the most appropriate therapies for their patients
Clinical laboratories and pathology groups aren’t the only healthcare providers being scrutinized for cost cutting and workflow efficiencies. Physicians ordering genetic tests are now in the spotlight thanks to a study of genetic test misordering by one healthcare institution.
In her award-winning presentation, “Genetic Testing Costs and Compliance with Clinical Best Practices,” given at the 2016 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG), Kathleen Ruzzo, MD, revealed some startling facts to the attendees. Ruzzo is an obstetrics and gynecology (OB-GYN) resident at the Naval Medical Center (NMC) in San Diego. She and a team of NMC researchers had reviewed all genetic tests ordered during a 3-month period. They found that more than one-third of the genetic tests examined were unnecessary and had led to more than $20,000 in additional healthcare expenditures. This got the attention of the ACOG, which awarded her 1st prize.
Critical Importance of Staying Informed on Genetic Tests
The researchers examined 114 charts that contained billing codes for genetic tests. They evaluated the charts for compliance with practice guidelines and completed a cost analysis of the tests. The tests were classified per GeneReviews guidelines and were labeled as:
Appropriate;
Misordered/Not Indicated;
Misordered/False Reassurance; or
Misordered/Inadequate.
GeneReviews is an online database focusing on information, diagnosis, management, and counseling of single-gene disorders. It is published by the National Center for Biotechnology Information.
The researchers found that:
44 of the 114 charts examined (39%) were misordered based on the guidelines;
24 of the tests were labeled as misordered/not indicated;
Eight tests were classified as misordered/false reassurance; and
12 tests were determined to be misordered/inadequate.
“We know there is an ever-expanding number of genetic tests available for clinicians to order, and there is more direct marketing to the patient,” stated Ruzzo in an Ob. Gyn. News article. “It can be difficult to stay on top of that as we have so many different clinical responsibilities.”
Kathleen Ruzzo, MD (above right) and Monica Lutgendorf, MD (above left) of the Naval Medical Center in San Diego, reviewed 114 genetic tests ordered during a three-month period. They discovered that 39% of the tests were misordered according to guidelines, costing a total of $75,000. (Photo copyright: Naval Medical Center.)
The actual testing was performed by Laboratory Corporation of America and occurred over a three-month period. The seven common genetic tests that were reviewed were tests for:
The cost analysis of the tests revealed that $20,000 could have been saved by following the GeneReviews guidelines. The total costs affiliated with the 114 tests reached $75,000. Potential savings were thus 26.6% of the total cost of the genetic tests involved in this study. In many clinical settings, if pathologists and medical laboratory managers could help physicians better utilize genetic tests while reducing the cost of such testing by almost 27%, that would be a major contribution. Plus, patients would be getting better care.
Ordering the Right Genetic Test Saves Money and Protects Patients
According to the National Institutes of Health (NIH), costs affiliated with genetic tests can range from less than $100 to more than $2,000 depending on the type and intricacy of the test. The NIH notes that many insurance companies will pay for genetic testing if ordered by a physician.
Ruzzo also shared that many of her cohorts were surprised at the results of the research.
“I think it opened a lot of people’s eyes … to be more meticulous about [genetic] testing and to ask for help when you need help,” she stated in the Ob. Gyn. News article. “Having trained individuals, reviewing genetic tests could save money in the healthcare system more broadly. We could also approve the appropriate testing for the patient.”
Ruzzo did admit there were limitations to the study; the researchers only looked at small amounts of tests for a short period and they did not concentrate on the consequences of the misordering to the patients.
Monica Lutgendorf, MD, Maternal Fetal Medicine Physician at the Naval Medical Center, was one of the coauthors of the paper. In the Ob. Gyn. News article, she described the findings as “a call to action in general for ob-gyns to get additional training and resources to handle the ever-expanding number of [genetic] tests.”
“I don’t think that this is unique to any specific institution. I think this is part of the new environment of practice that we’re in,” Lutgendorf concluded.
Due to the costs of genetic testing and the fact that so many physicians have not been able to keep up with all the latest advances in genetic medicine and testing, misordering will, most likely, continue to be a problem. Nevertheless, pathologists and clinical laboratory managers can serve a crucial role in helping physicians be more effective at selecting the correct genetic tests and assisting them in interpreting results to choose the most appropriate therapies for their patients.
For information about this high-value webinar and to register, use this link (or copy this URL and paste into your browser: https://ddaily.wpengine.com/webinar/simple-swift-approaches-to-lab-test-utilization-management-proven-ways-for-your-clinical-laboratory-to-use-data-and-collaborations-to-add-value.)
