Schwan’s concerns about inaccurate or unreliable COVID-19 serology tests were supported when the FDA issued more restrictive rules for these medical laboratory tests on May 4
During a conference call with investors about the company’s first-quarter results, Schwan said of the recently-launched COVID-19 antibody assays, “These tests are not worth anything, or have very little use,” according to reporting from Reuters and other publications. “Some of these companies, I tell you, this is ethically very questionable to get out with this stuff.”
On May 3, Roche announced that its own Elecsys Anti-SARS-CoV-2 antibody test for SARS-CoV-2, the coronavirus that causes the COVID-19 illness, had obtained an emergency use authorization (EUA) from the federal Food and Drug Administration (FDA). In its news release, Roche stated that “the serology test has a specificity greater than 99.8% and sensitivity of 100% (14 days post-PCR confirmation).”
In a separate interview with Bloomberg, Schwan said about antibody testing, “It is very important to pick the right test and then to validate those tests with enough patients.” He then returned to the issue of poor quality in some antibody tests for the SARS-CoV-2 virus, saying, “Unfortunately, there are a number of tests already out there in the market which are not reliable simply because they haven’t been tested sufficiently.”
In reference to the initial release of serological COVID-19 antibody tests, CEO Severin Schwan (above) said during Roche Holding’s first quarter earnings call that, “It’s a disaster. These tests are not worth anything, or have very little use,” reported CNBC. He added, “This is really what matters. Every kind of amateur could produce an antibody test. The two of us could do it overnight in the garage. That’s not the problem. The question is, does it really work? And for that, you have to do testing and validation.” (Photo copyright: Reuters/Arnd Wiegmann.)
A ‘Wild West’ of Unregulated Assays
Prior to issuing tougher rules for how a manufacturer can market a COVID-19 serological test, the FDA had listed about 200 serological tests designed to identify antibodies produced by the human immune system in response to a SARS-CoV-2 infection. This is the process of seroconversion, which is the development of detectable antibodies in a patient’s blood against a pathogen. Detection of IgG antibodies indicates exposure to SARS-CoV-2, according to ARUP Laboratories.
Public health experts have raised questions about the proliferation of such tests for the new coronavirus. Under the FDA’s previous March 16 rules—which were more relaxed than those FDA applied when granting EUAs—the agency was swamped with requests to review more than 200 COVID-19 antibody tests. The looser regulations resulted in nearly no oversight of those tests, reported the Associated Press (AP).
In comments to the AP, Eric Blank, DrPH, Senior Director of Public Health Systems and Programs for the Association for Public Health Laboratories (APHL), said, “Right now it’s a wild west show out there. It really has created a mess that’s going to take a while to clean up.”
“In the meantime,” Blank added, “you’ve got a lot of companies marketing a lot of stuff and nobody has any idea of how good it is.” Blank confirmed to Dark Daily that he made these comments and stands by them.
Calls for Closer Scrutiny of Serological Antibody Tests
In response to the FDA’s March 16 rules for COVID-19 serology tests, APHL requested the federal agency to review its looser approach to reviewing these tests. The impact of the FDA’s much tougher COVID-19 serological testing rules released on May 4 was immediate.
In a press release issued on May 2, the FDA said, “to date, the FDA has authorized 105 tests under EUAs, which include 92 molecular tests, 12 antibody tests, and one antigen test.”
Clinical laboratories in the United States still face difficult challenges if they plan to launch their own COVID-19 serology testing programs. They must select one or more tests from among the antibody and antigen tests that have an FDA EUA. However, data for each of these tests is not as comprehensive as is the data for diagnostic test kits reviewed by the FDA and cleared for market under the pre-market approval process.
This webinar was conducted by James O. Westgard, PhD, and Sten Westgard of Westgard QC, Inc., and the full program is available for free download by clicking here, or by placing this URL in your web browser: https://www.darkdaily.com/webinar/quality-issues-your-clinical-laboratory-should-know-before-you-buy-or-select-covid-19-serology-tests/.
In the webinar recording, the Westgards provide a detailed overview of what elements are required for a clinical lab to have confidence that its COVID-19 serology testing program is producing accurate, reliable results. They explain that labs must understand the unique aspects of the populations they are testing in their communities. All of these factors can then be used by labs to evaluate the different COVID-19 serology tests available for them to purchase, and to select the test that best fits their lab’s capabilities and the characteristics of the patient population that will be tested.
Another important requirement for clinical laboratories to understand is the list of steps necessary to bring up a COVID-19 serological testing program. That starts with validating the test, then bringing it into daily production. As that happens, issues associated with quality control (QC), proficiency testing (PT), and regulatory compliance take center stage, so that the clinical lab has high confidence in the accuracy and reproducibility of the COVID-19 serology test results they are using in patient care or in support of employers who are screening employees for COVID-19.
To register for the June 11 webinar, click here, or place this URL in your web browser: https://www.darkdaily.com/webinar/achieving-high-confidence-levels-in-the-quality-and-accuracy-of-your-clinical-labs-chosen-covid-19-serology-tests/.
New COVID-19 Intelligence from Dark Daily
Announcing Dark Daily’s new COVID-19 STAT Intelligence Briefings! This free service for clinical laboratories, anatomic pathology groups, and diagnostics companies features:
daily breaking news,
business intelligence, and
innovations that clinical labs are using to respond to the COVID-19 pandemic.
This critical information includes effective ways labs can restore their cash flow to pre-pandemic levels and get test claims paid by government and private payers.
One popular feature is the COVID-19 Live! conference calls that happen every Tuesday and Thursday for 30 minutes at 1 PM, EDT. Visit the COVID-19 STAT Intelligence Briefings website and join us for the live calls.
Genetic data captured by this new technology could lead to a new understanding of how different types of cells exchange information and would be a boon to anatomic pathology research worldwide
What if it were possible to map the interior of cells and view their genetic sequences using chemicals instead of light? Might that spark an entirely new way of studying human physiology? That’s what researchers at the Massachusetts Institute of Technology (MIT) believe. They have developed a new approach to visualizing cells and tissues that could enable the development of entirely new anatomic pathology tests that target a broad range of cancers and diseases.
Scientists at MIT’s Broad Institute and McGovern Institute for Brain Research developed this new technique, which they call DNA Microscopy. They published their findings in Cell, titled, “DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction.”
Joshua Weinstein, PhD, a postdoctoral associate at the Broad Institute and first author of the study, said in a news release that DNA microscopy “is an entirely new way of visualizing cells that captures both spatial and genetic information simultaneously from a single specimen. It will allow us to see how genetically unique cells—those comprising the immune system, cancer, or the gut for instance—interact with one another and give rise to complex multicellular life.”
The news release goes on to state that the new technology “shows
how biomolecules such as DNA and RNA are organized in cells and tissues,
revealing spatial and molecular information that is not easily accessible
through other microscopy methods. DNA microscopy also does not require
specialized equipment, enabling large numbers of samples to be processed
simultaneously.”
The images above, taken from the MIT study, compares optical imaging of a cell population (left) with an inferred visualization of the same cell population based on the information provided by DNA microscopy (right). Scale bar = 100 μm (100 micrometers). This technology has the potential to be useful for anatomic pathologists at some future date. (Photo and caption copyrights: Joshua Weinstein, PhD, et al/Cell.)
New Way to Visualize Cells
The MIT researchers saw an opportunity for DNA microscopy to
find genomic-level cell information. They claim that DNA microscopy images
cells from the inside and enables the capture of more data than with
traditional light microscopy. Their new technique is a chemical-encoded
approach to mapping cells that derives critical genetic insights from the
organization of the DNA and RNA in cells and tissue.
And that type of genetic information could lead to new precision medicine treatments for chronic disease. New Atlas notes that “ Speeding the development of immunotherapy treatments by identifying the immune cells best suited to target a particular cancer cell is but one of the many potential application for DNA microscopy.”
In their published study, the scientists note that “Despite enormous progress in molecular profiling of cellular constituents, spatially mapping [cells] remains a disjointed and specialized machinery-intensive process, relying on either light microscopy or direct physical registration. Here, we demonstrate DNA microscopy, a distinct imaging modality for scalable, optics-free mapping of relative biomolecule positions.”
How DNA Microscopy Works
The New York Times (NYT) notes that the advantage of DNA microscopy is “that it combines spatial details with scientists’ growing interest in—and ability to measure—precise genomic sequences, much as Google Street View integrates restaurant names and reviews into outlines of city blocks.”
And Singularity Hub notes that “ DNA microscopy, uses only a pipette and some liquid reagents. Rather than monitoring photons, here the team relies on ‘bar codes’ that chemically tag onto biomolecules. Like cell phone towers, the tags amplify, broadcasting their signals outward. An algorithm can then piece together the captured location data and transform those GPS-like digits into rainbow-colored photos. The results are absolutely breathtaking. Cells shine like stars in a nebula, each pseudo-colored according to their genomic profiles.”
“We’ve used DNA in a way that’s mathematically similar to photons in light microscopy,” Weinstein said in the Broad Institute news release. “This allows us to visualize biology as cells see it and not as the human eye does.”
In their study, researchers used DNA microscopy to tag RNA
molecules and map locations of individual human cancer cells. Their method is
“surprisingly simple” New Atlas reported. Here’s how it’s done,
according to the MIT news release:
Small synthetic DNA tags (dubbed “barcodes” by the MIT team) are added to biological samples;
The “tags” latch onto molecules of genetic material in the cells;
The tags are then replicated through a chemical reaction;
The tags combine and create more unique DNA labels;
The scientists use a DNA sequencer to decode and reconstruct the biomolecules;
A computer algorithm decodes the data and converts it to images displaying the biomolecules’ positions within the cells.
The visualization above was created from data gathered by DNA microscopy, which peers inside individual cells. It demonstrates how DNA microscopy enables scientists to identify different cells (colored dots) within a sample—with no prior knowledge of what the sample looks like. (Photo and caption copyright: Joshua Weinstein, PhD, et al./Cell.)
“The first time I saw a DNA microscopy image, it blew me away,” said Aviv Regev, PhD, a biologist at the Broad Institute, a Howard Hughes Medical Institute (HHMI) Investigator, and co-author of the MIT study, in an HHMI news release. “It’s an entirely new category of microscopy. It’s not just a technique; it’s a way of doing things that we haven’t ever considered doing before.”
Precision Medicine Potential
“Every cell has a unique make-up of DNA letters or genotype. By capturing information directly from the molecules being studied, DNA microscopy opens up a new way of connecting genotype to phenotype,” said Feng Zhang, PhD, MIT Neuroscience Professor,
Core Institute Member of the Broad Institute, and
Investigator at the McGovern Institute for Brain Research at MIT, in the HHMI
news release.
In other words, DNA microscopy could someday have applications in precision medicine. The MIT researchers, according to Stat, plan to expand the technology further to include immune cells that target cancer.
The Broad Institute has applied for a patent on DNA
microscopy. Clinical laboratory and anatomic pathology group leaders seeking
novel resources for diagnosis and treatment of cancer may want to follow the MIT
scientists’ progress.
Scientists with Francis Crick Institute and Ragon Institute have successfully created human antibodies in vitro that can be made to recognize specific antigens in the human body; Could lead to new treatments for cancer and other infectious diseases
It’s been long-recognized that the ability to design human antibodies customized to recognize specific antigens could be a game-changer in the diagnosis and treatment of many diseases. It would enable the creation of useful new clinical laboratory tests, vaccines, and similar therapeutic modalities.
Now an international research team has published the findings of its novel technique that was developed to generate human antibodies in vitro. The research was conducted at the Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), Harvard, and the Francis Crick Institute in London.
Antibodies and antigens are used in a large number of clinical laboratory and anatomic pathology tests and assays. In many cases, animal antibodies/antigens are used in test kits because they attract and bind to specific human antibodies/antigens that are biomarkers for diagnoses. Thus, as this technology is validated and further developed, it could be the source of useful biomarkers for lab tests as well as for vaccines.
Antibodies—also referred to as immunoglobulins—are made by the body’s B-lymphocytes (B cells) in response to antigens, such as bacteria, viruses, or other harmful substances. Each antibody has a special bearing on a particular antigen. For example, the human immunodeficiency virus (HIV) antibody and HIV antigen (p24) test screens and diagnoses people for HIV infection, explained LabTestsOnline.
Many medical laboratory tests use animal antibodies and antigens. But what if human antibodies could be generated and stimulated to recognize specific human antigens? That’s what the researchers believe they have done, according to a press release.
The Ragon Institute at MGH, MIT, and Harvard (above) was established in 2009 to find an HIV vaccine and to be a worldwide leader in the study of immunology. The Francis Crick Institute, formed in 2015, is a biomedical research institute using biology to understand health and disease. (Photo copyright: The Ragon Institute.)
The researchers know the novel technique they developed for generating human antibodies in vitro needs further development and validation. If this happens, the technique could one day be the source of useful biomarkers for medical lab tests, and may be a way to prevent infectious diseases.
“Specifically, it should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals,” said Facundo D. Batista, PhD, in the press release. Batista is Principle Investigator with the Ragon Institute and led the research teams. “In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens.”
Researchers Aim to Make Human Antibodies in Medical Laboratory
This international team of researchers sought to replicate in the lab—using patient blood samples—a natural human process for creation of antibodies from B cells. This is the process they wished to replicate:
· Antibodies are made by the body’s B cells;
· An antigen molecule is recognized by a B cell;
· Plasma cells (able to secrete antibodies) develop;
· An antibody binds to a particular antigen to fight an infection.
“B lymphocytes (B cells) play a critical role in adaptive immunity, providing protection from pathogens through the production of specific antibodies. B cells recognize and respond to pathogen-derived antigens through surface B cell receptors,” the researchers wrote in The Journal of Experimental Medicine (JEM).
Nanoparticles Key to the Approach
But finding an exact antigen is only one part of the B cell’s job. In the lab, B cells also need a trigger that enables them to grow and develop into plasma cells, which are key to fighting disease, the researchers noted.
“The in vitro activation of B cells in an antigen-dependent manner is difficult to achieve,” the authors stated in the JEM. “To overcome limitations, we developed a novel in vitro strategy to stimulate human B cells with streptavidin nanoparticles conjugated to both CpG and antigen. B cells producing antigen-specific antibodies were identified, quantified, and characterized to determine the antibody repertoire.”
According to the press release, “CpG oligonucleotides internalize into B cells that recognize the specific antigen.”
The statement, which garnered worldwide attention, noted the following steps taken by the researchers:
· B cells from patient blood samples were isolated;
· Then, they were treated with tiny nanoparticles coated with both CpG oligonucleotides and the right antigen;
· These DNA molecules are unique, because they can activate toll-like receptor 9 (TLR9);
· TLR9 develops into antibody-secreting plasma cells.
Results: Antibodies for Tetanus, Influenza, HIV
This method, according to the scientists, could be used in further research to develop antibodies to treat infectious diseases and cancer.
· “The team successfully demonstrated their approach using various bacterial and viral antigens, including the tetanus toxoid and proteins from several strains of influenza A;
· “In each case, the researchers were able to produce specific, high-affinity antibodies in just a few days. Some of the anti-influenza antibodies generated by the technique recognized multiple strains of the virus and were able to neutralize its ability to infect cells;
· “The procedure does not depend on the donors having been previously exposed to any of these antigens through vaccination or infection; and,
· “Researchers were able to generate anti-HIV antibodies from B cells isolated from HIV-free patients.”
Research Suggests More Possibilities
While this highly scientific study may not be on the radar of most anatomic pathologists and medical laboratory leaders at the moment, it holds enormous promise to produce cures for infectious disease and more effective cancer treatments. This research project also demonstrates how new techniques using antibodies have the potential to create an entirely new generation of clinical laboratory assays that improve diagnostic accuracy and better inform physicians when they consider the most appropriate therapies for their patients.
Using 3D printing and a chemical heat source, University of Pennsylvania researchers have created a proof-of-concept for an affordable Zika test that returns results in just 40 minutes
There’s a gap in Zika virus testing that researchers at the University of Pennsylvania hope to fill. That gap is a point-of-care test for the Zika virus that can produce a fast and accurate result, whether in developed nations or in developing countries that don’t have many state-of-the art clinical laboratories.
The VirScan test gives doctors insight into a patient’s lifetime exposure to viruses and thus may be developed into a useful medical laboratory test
Scientists and pathologists are learning that blood is like a time capsule, holding precious information about exposure to viruses over the years—chickenpox at five, mononucleosis at 18, flu at 40. You get the idea.
Now, researchers at Howard Hughes Medical Institute (HHMI) have found a way to tap that entire data stream, so to speak. An inexpensive blood test, they say, reveals every virus that has passed through the body over time.
New Discoveries Could Lead to a Useful Clinical Laboratory Test
The testing method, called VirScan by researchers, is an efficient alternative to current medical laboratory tests that test for specific viruses one at a time, according to an HHMI news statement about the new technology. (more…)
