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University of Chicago Study Determines Certain Gut Bacteria Can Help Prevent Food Allergies and Other Gastrointestinal Illnesses

With further research, clinical laboratories may soon be performing macrobiotic testing to measure certain bacterial levels in patients’ gut bacteria

New insights from the University of Chicago (UChicago) into how human microbiota (aka, gut bacteria) play a role in food allergies has the potential to change the way a number of gastrointestinal health conditions are diagnosed and treated. This would give microbiologists and clinical laboratories a greater role in helping physicians diagnose, treat, and monitor patients with these health issues.

Past research has shown that certain gut bacteria can prevent antigens that trigger allergic reactions from entering the bloodstream. For example, Clostridium bacteria in the stomach produce a short-chain fatty acid known as butyrate, a metabolite that promotes the growth of healthy bacteria in the gut. This helps keep the microbiome in balance.

One way butyrate is created in the gut is through the fermentation of fiber. However, a lack of fiber in the diet can deplete the production of butyrate and cause the microbiome to be out of balance. When this happens, a state known as dysbiosis occurs that disrupts the microbiome and can lead to food allergies. 

Without butyrate, the gut lining can become permeable and allow food to leak out of the gastrointestinal tract and into the body’s circulatory system. This reaction can trigger a potentially fatal anaphylactic response in the form of a food allergy. Thus, eating enough fiber is critical to the production of butyrate and to maintaining a balanced microbiome.

But today’s western diet can be dangerously low in soluble fiber. Therefore, the scientists at the University of Chicago have developed “a special type of polymeric molecule to deliver a crucial metabolite produced by these bacteria directly to the gut, where it helps restore the intestinal lining and allows the beneficial bacteria to flourish. … these polymers, called micelles, can be designed to release a payload of butyrate, a molecule that is known to help prevent food allergies, directly in the small and large intestines,” according to a UChicago news release.

This will be of interest to microbiologists, in particular. It’s another example of researchers connecting a specific species of bacteria in the human microbiome to a specific benefit.

The University of Chicago scientists published their findings in the journal Nature Biomedical Engineering titled, “Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles.”

Cathryn Nagler, PhD

“It’s very unlikely that butyrate is the only relevant metabolite, but the beauty of this platform is that we can make polymers with other microbial metabolites that could be administered in conjunction with butyrate or other therapies,” said Cathryn Nagler, PhD (above), Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at UChicago and a senior author of the study. “So, the potential for the polymer platform is pretty much wide open.” As further research validates these findings, clinical labs are likely to be doing microbiomic testing to monitor these therapies. (Photo copyright: University of Chicago.)

Restoring Butyrate in the Gut

One way to treat this anomaly has been through a microbiota transplant—also called a fecal biota transplant—where the administration of a solution of fecal matter is transplanted from a donor into the intestinal tract of the recipient. This transplant alters the recipient’s gut microbial composition to a healthier state, but it has had mixed results. 

So, the UChicago researchers went in another direction (literally). They created an oral solution of butyrate and administered it to mice in the lab. The purpose of the solution was to thwart an allergic reaction when the mice were exposed to peanuts. 

But there was a problem with their oral solution. It was repulsive.

“Butyrate has a very bad smell, like dog poop and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it,” Shijie Cao, PhD, Postdoctoral Scientist at the Pritzker School of Molecular Engineering at UChicago and one of the researchers who worked on the project, told Medical News Today.

The researchers developed a new configuration of polymers that masked the butyrate. They then delivered these polymer micelles directly into the digestive systems of mice that lacked healthy gut bacteria or a proper gut linings.

The treatment restored the microbiome by increasing the production of peptides that obliterate harmful bacteria. This allowed more of the beneficial butyrate-producing bacteria to emerge, which protected the mice from an anaphylactic reaction to peanuts and even reduced the symptom severity in an ulcerative colitis model. 

“We were delighted to see that our drug both replenished the levels of butyrate present in the gut and helped the population of butyrate-producing bacteria to expand,” said Cathryn Nagler, PhD, Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at the University of Chicago and a senior author of the study, in the press release. “That will likely have implications not only for food allergy and inflammatory bowel disease (IBD), but also for the whole set of non-communicable chronic diseases that have been rising over the last 30 years, in response to lifestyle changes and overuse of antibiotics in our society.”

Future Benefits of UChicago Treatment

According to data from the Asthma and Allergy Foundation of America, about 20 million Americans suffered from food allergies in 2021. This includes approximately 16 million (6.2%) of adults and four million (5.8%) of children. The most common allergens for adults are shellfish, peanuts, and tree nuts, while the most common allergens for children are milk, eggs, and peanuts. 

The best way to prevent an allergic reaction to a trigger food is strict avoidance. But this can be difficult to ensure outside of the home. Therefore, scientists are searching for ways to prevent food allergies from happening in the first place. The micelle technology could be adapted to deliver other metabolites and molecules which may make it a potential platform for treating allergies as well as other inflammatory gastrointestinal diseases

“It’s a very flexible chemistry that allows us to target different parts of the gut,” said Jeffrey Hubbell, PhD, Eugene Bell Professor in Tissue Engineering and Vice Dean and Executive Officer at UChicago’s Pritzker School of Molecular Engineering and one of the project’s principal investigators, in the UChicago news release. “And because we’re delivering a metabolite like butyrate, it’s antigen-agnostic. It’s one agent for many different allergic indications, such as peanut or milk allergies. Once we begin working on clinical trials, that will be a huge benefit.”

Nagler and Hubbell have co-founded a company called ClostraBio to further the development of butyrate micelles into a commercially available treatment for peanut and other food allergies. They hope to begin clinical trials within the next 18 months and expand the technology to other applications as well.  

Further research and clinical trials are needed to prove the validity of using polymer micelles in the treatment of diseases. But it is possible that clinical laboratories will be performing microbiomic testing in the future to help alleviate allergic reactions to food and other substances.

—JP Schlingman

Related Information:

Peanut and Food Allergies May Be Reversed with Compound Produced by Healthy Gut Bacteria

Time Release Polymers Deliver Metabolites to Treat Peanut Allergy and Colitis

Food Allergies: Reversing the Old, Preventing the New with Gut Bacteria

Scientists Reverse Food Allergies by Targeting the Microbiome

Polymers Help Protect Mice from Anaphylactic Reaction to Peanuts, UChicago Research Finds

Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles

New American Gastroenterological Association Guidelines for Managing Crohn’s Disease Suggest More Clinical Laboratory Tests and Fewer Colonoscopies

As doctors become more familiar with using biomarkers to monitor Crohn’s disease, clinical laboratories may play a greater role in that process

New evidence-based guidelines from the American Gastroenterological Association (AGA) that call for using specific biomarkers to help manage Crohn’s disease (CD) may decrease the number of invasive procedures patients must undergo and increase the role clinical laboratories play in monitoring the disease.

The new AGA guidelines “recommend using the C-reactive protein (CRP) biomarker in blood and the fecal calprotectin (FCP) biomarker in stool to measure inflammation levels and assess whether Crohn’s disease is in remission or active,” Medical News Today reported.

Crohn’s disease is a chronic inflammatory bowel disease (IBD) that causes inflammation in the digestive tract, primarily in the small and large intestine. The cause of the disease is unknown, but genetics may play a role.

Typically, CD patients must undergo repeated colonoscopies to monitor the disease’s progression or remission. This has long been standard practice. Now, however, “AGA recommends the use of biomarkers in addition to colonoscopy and imaging studies,” according to an AGA news release. This hints at a greater role for clinical laboratories in helping physicians manage patients with Crohn’s Disease.

“Patients’ symptoms do not always match endoscopic findings, so biomarkers are a useful tool to understand and monitor the status of inflammation and guide decision making in patients with Crohn’s disease,” said gastroenterologist Siddharth Singh, MD, Assistant Professor of Medicine at UC San Diego Health and a co-author of the new AGA guidelines.

The AGA’s new guidelines demonstrate how medical science is generating new insights about how multiple biomarkers can be associated for diagnosis/management of a disease in ways that change the standard of care, particularly if it can reduce invasive procedures for the patient by the use of less invasive methods (such as a venous blood draw instead of a colonoscopy).

The AGA published its new guidelines in the journal Gastroenterology titled, “AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn’s Disease.”

Ashwin Ananthakrishnan MD

“Based on this guideline, biomarkers are no longer considered experimental and should be an integral part of inflammatory bowel disease care,” Ashwin Ananthakrishnan MD (above), a gastroenterologist at Massachusetts General Hospital and co-author of the guidelines, told Medical News Today. Under the new AGA guidelines, clinical laboratories will play a greater role in helping patients monitor their disease. (Photo copyright: Massachusetts General Hospital.)

Patient’s Needs Determine Biomarker vs Endoscopy Monitoring

AGA’s new guidelines could give patients a more comfortable, cost-effective, and possibly more efficient treatment plan to manage their Crohn’s disease. That’s even true if a patient’s Crohn’s disease is in remission.

With these new guidelines, Crohn’s disease patients in remission would only need their biomarkers to be checked every six to 12 months. Patients with active symptoms would need their biomarkers checked roughly every two to four months.

Biomarker testing can be seen as a useful addition to Crohn’s disease care rather than a full replacement of other forms of care. For example, the new AGA guidelines do not fully omit imaging studies and colonoscopies from treatment. Rather, they are recommended in treatment plans based on the patient’s needs.

In their Gastroenterology paper, the AGA authors wrote, “A biomarker-based monitoring strategy involves routine assessment of symptoms and noninvasive biomarkers of inflammation in patients with CD in symptomatic remission to inform ongoing management. In this situation, normalization of biomarkers is an adequate treatment target—asymptomatic patients with normal biomarkers would continue current management without endoscopy, whereas those with elevated biomarkers would undergo endoscopy.”

Fecal Matter Biomarkers

In speaking with Medical News Today on the benefits of using fecal biomarkers to assess a patient’s disease maintenance, gastroenterologist Jesse Stondell, MD, an Associate Clinical Professor at UC Davis Health, said, “If we start a patient on therapy, they’re not responding appropriately, they’re still having a lot of symptoms, we can check that fecal calprotectin test and get a very quick sense of if things are working or not.

“If the calprotectin is normal, it could be reassuring that there may be other reasons for their symptoms, and that the medicine’s working. But if they have symptoms, and a calprotectin is elevated, that’s a signal that we have to worry the medicine is not working. And that we need to change therapy in that patient,” he added.

“This is a win for Crohn’s disease patients,” Ashwin Ananthakrishnan, MD, a gastroenterologist at Massachusetts General Hospital and co-author of the AGA’s new guidelines, told Medical News Today. “Biomarkers are usually easier to obtain, less invasive, more cost-effective than frequent colonoscopies, and can be assessed more frequently for tighter disease control and better long-term outcomes in Crohn’s disease.”

Clinical laboratories should expect these guidelines to increase demand for the processing of blood or fecal matter biomarker testing. As Crohn’s disease monitoring becomes more dependent on biomarker testing, clinical labs will play a critical role in that process.

—Ashley Croce

Related Information:

Fewer Colonoscopies? New Crohn’s Guidelines Emphasize Blood, Stool Tests as Management Tool

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn’s Disease

Biomarker- vs Endoscopy-Based Monitoring Strategy in Crohn’s Disease

First Comprehensive Guideline on Using Biomarkers for Monitoring Crohn’s Disease

National Library of Medicine: Crohn’s Disease

Crohn’s Disease Is on the Rise

UW Medicine Researchers Identify Blood Cell Genetic Mutations That Can Disrupt Liquid Biopsy Results

The discovery is yet another factor that must be considered when developing a liquid biopsy test clinical laboratories can use to detect cancer

How often do disruptive elements present in Liquid biopsies result in misdiagnoses and unhelpful drug therapies for cancer? Researchers at the University of Washington School of Medicine (UW Medicine) in Seattle wanted to know. And the results of their study provide another useful insight for pathologists about the elements that circulate in human blood which must be understood so that liquid biopsy tests can be developed that are not affected by that factor.

Based on their case series study of 69 men with advanced prostate cancer, the UW Medicine researchers determined that 10% of men have a clonal hematopoiesis of indeterminate potential (CHIP) that can “interfere” with liquid biopsies and cause incorrect reports and unneeded prostate cancer treatment, according to their paper published in the journal JAMA Oncology.

The process of clonal hematopoiesis occurs when hematopoietic stem cells generate blood cells that mimic blood mutations in the same way as hematopoiesis, Labroots explained in “Potential Problems with Liquid Biopsies.” Hence, the word “clonal” in the description. 

The UW Medicine researchers advised testing for “variants in the cell-free DNA (cfDNA)” shed in blood plasma to enable appropriate treatment for people with already diagnosed prostate cancer, noted to a UW Medicine news release.

According to pathologist Colin Pritchard, MD, PhD, Associate Professor of Laboratory Medicine and Pathology at the UW Medicine, who led the research team, “clonal hematopoiesis can interfere with liquid biopsies. For example, mutations in the genes BRCA1, BRCA2, and ATM have been closely linked to cancer development.

“Unfortunately, these same genes are also commonly mutated as a result of clonal hematopoiesis,” he told Labroots. Pritchard is also Head of the Genetics Division of Laboratory Medicine at UW Medicine, Director of Clinical Diagnostics for the Brotman Baty Institute for Precision Medicine, and Co-Director of the Genetics and Solid Tumors Laboratory at the University of Washington Medical Center.

“The good news is that, by looking at the blood cellular compartment, you can tell with pretty good certainty whether something is cancer, or something is hematopoiesis,” he said in the news release.

What Does CHIP Interference Mean to a Clinical Laboratory Blood Test?

In their published study, the UW Medicine researchers stressed the “urgent need to understand cfDNA testing performance and sources of test interferences” in light of recent US Food and Drug Administration (FDA) clearance of two PARP inhibitors (PARPi) for prostate cancer:

“We found that a strikingly high proportion of DNA repair gene variants in the plasma of patients with advanced prostate cancer are attributable to CHIP,” the researchers wrote. “The CHIP variants were strongly correlated with increased age, and even higher than expected by age group.

“The high rate of CHIP may also be influenced by prior exposure to chemotherapy,” they added. “We are concerned that CHIP interference is causing false-positive cfDNA biomarker assessments that may result in patient harm from inappropriate treatment, and delays in delivering alternative effective treatment options.

“Without performing a whole-blood control, seven of 69 patients (10%) would have been misdiagnosed and incorrectly deemed eligible for PARP-inhibitor therapy based on CHIP interference in plasma. In fact, one patient in this series had a BRCA2 CHIP clone that had been previously reported by a commercial laboratory testing company with the recommendation to use a PARPi. To mitigate these risks, cfDNA results should be compared to results from whole-blood control or tumor tissue,” the researchers concluded.

To find the clinically relevant CHIP interference in prostate cancer cfDNA testing, researchers used the UW-OncoPlex assay (developed and clinically available at UW Medicine). The assay is a multiplexed next-generation sequencing panel aimed at detecting mutations in tumor tissues in more than 350 genes, according to the UW Medicine Laboratory and Pathology website. 

“To improve cfDNA assay performance, we developed an approach that simultaneously analyzes plasma and paired whole-blood control samples. Using this paired testing approach, we sought to determine to what degree CHIP interferes with the results of prostate cancer cfDNA testing,” the researchers wrote in JAMA Oncology

Men May Receive Unhelpful Prostate Cancer Drug Therapies

The research team studied test results from 69 men with advanced prostate cancer. They analyzed patients’ plasma cfDNA and whole-blood control samples.

Tumor sequencing enabled detection of germline (cells relating to preceding cells) variants from CHIP clones.

The UW Medicine study suggested CHIP variants “accounted for almost half of the somatic (non-germline) DNA repair mutations” detected by liquid biopsy, according to the news release.

Colin Pritchard, MD, PhD
>
“About half the time when the plasma is thought to contain a mutation that would guide therapy with these drugs, it actually contains CHIP variants, not prostate cancer DNA variants. That means that in about half of those tested, a patient could be told that he should be administered a drug that is not indicated to treat to his cancer,” said Colin Pritchard, MD, PhD, pathologist and Associate Professor of Laboratory Medicine and Pathology at UW Medicine in the new release. (Photo copyright: University of Washington School of Medicine.)

Other detailed findings of the UW Medicine Study:

  • CHIP variants of 2% or more were detected in cfDNA from 13 of 69 men.
  • Seven men, or 10%, having advanced prostate cancer “had CHIP variants in DNA repair genes used to determine PARPi candidacy.
  • CHIP variants rose with age: 0% in those 40 to 50; 12.5% in men 51 to 60; 6.3% in those 61 to 70; 20.8% in men 71 to 80; and 71% in men 81 to 90.
  • Whole-blood control made it possible to distinguish prostate cancer variants from CHIP interference variants.

“Men with prostate cancer are at high risk of being misdiagnosed as being eligible for PARPi therapy using current cfDNA tests; assays should use a whole-blood control sample to distinguish CHIP variants from prostate cancer,” the researchers wrote in JAMA Oncology.

Liquid Biopsies Are ‘Here to Stay’

Surgical oncologist William Cance, MD, Chief Medical and Scientific Officer, American Cancer Society (ACS) in Atlanta, recognizes the challenge of tumor biology to liquid biopsies. 

“Genetic abnormalities are only one piece of the puzzle. We need to look comprehensively at tumors for the best therapy, from their metabolic changes and protein signatures in the blood to the epigenetic modifications that may occur, as cancers take hold,” he told Oncology Times. “It’s not just shed DNA in the blood.”

The UW Medicine study demonstrates the importance of understanding how all elements in liquid biopsies interact to affect clinical laboratory test results.

“I think liquid biopsies are here to stay,” Cance told Oncology Times. “They’re all part of precision medicine, tailored to the individual.”

Donna Marie Pocius

Related Information:

Association of Clonal Hematopoiesis in DNA Repair Genes with Prostate Cancer Plasma Cell-free DNA Testing Interference

Potential Problems with Liquid Biopsies

Blood Cell Mutations Confound Prostate Cancer Liquid Biopsy

Pursing and Perfecting Use of Liquid Biopsies in Cancer Early Detection

Researchers at Harvard’s Massachusetts General Hospital Develop a Non-Invasive Liquid Biopsy Blood Test to Detect and Monitor Common Brain Tumors in Adults

Using Extracellular Vesicles, Researchers Highlight Viability of Liquid Biopsies for Cancer Biomarker Detection in Clinical Laboratories

New studies in UK and at Stanford University Show Lung Cancer Cells Circulating in Blood; Findings Could Make It Possible for Pathologists to Diagnose Cancer with ‘Liquid Biopsies’

Researchers Identify Antibodies That Could Be Protective Against Multiple Sarbecoviruses, Including SARS-CoV-2 and Its Variants

The antibodies target portions of the SARS-CoV-2 spike protein that resist mutation, potentially leading to better treatments and vaccines

One challenge in the battle against COVID-19 is the emergence of SARS-CoV-2 variants, especially the Delta variant, which may be more resistant to neutralizing antibodies compared with the original coronavirus. But now, scientists led by researchers at the Fred Hutchinson Cancer Research Center (Fred Hutch) in Seattle say they have identified antibodies that could be broadly protective against multiple sarbecoviruses, the subgenus that contains SARS-CoV-2 as well as SARS-CoV-1, the virus responsible for the 2002-2004 severe acute respiratory syndrome (SARS) outbreak.

In “SARS-CoV-2 RBD Antibodies That Maximize Breadth and Resistance to Escape,” the researchers described how they compared 12 antibodies obtained from patients infected with either SARS-CoV-2 or SARS-CoV-1. They pointed to one antibody in particular—S2H97—that could lead to development of new vaccines and therapies against current and future variants. It might even protect against sarbecoviruses that have not yet been identified, they wrote.

Unsaid in the news release about these research findings is the fact that these particular antibodies could eventually become useful biomarkers for clinical laboratory tests designed to help physicians determine which patients have these antibodies—and the protection from infection they represent—and which do not.

So far, however, S2H97 has only been tested in hamsters. But results are promising.

“This antibody, which binds to a previously unknown site on the coronavirus spike protein, appears to neutralize all known sarbecoviruses—the genus of coronaviruses that cause respiratory infections in mammals,” said Jay Nix, PhD, an affiliate in Berkeley Lab’s Biosciences Area and Beamline Director of the Molecular Biology Consortium at Berkeley Lab’s Advanced Light Source (ALS), in a Berkeley Lab news release. “And, due to the unique binding site on mutation-resistant part of the virus, it may well be more difficult for a new strain to escape,” he added.

The research team led by biochemist Tyler Starr, PhD, a postdoctoral fellow at Fred Hutch, also included researchers from Vir Biotechnology (NASDAQ:VIR), the University of Washington in Seattle, Washington University School of Medicine in St. Louis, and Lawrence Berkeley National Laboratory in Berkeley, Calif.

Mutation Resistance

Scientists have long known that the SARS-CoV-2 virus uses the spike protein to attach to human cells. The federal Centers for Disease Control and Prevention (CDC) notes that the variants have mutations in their spike proteins that make some of them more transmissible.

The Delta variant, the CDC notes, was the predominant variant in the US as of August 28, 2021. It “has been shown to have increased transmissibility, potential reduction in neutralization by some monoclonal antibody treatments, and reduction in neutralization by post-vaccination sera,” the agency states.

The key to S2H97, the researchers wrote, is that it targets a portion of the spike protein that is common among sarbecoviruses, and that is likely to be resistant to mutations.

The researchers used a variety of techniques to analyze how the 12 antibodies bind to the virus. They “compiled a list of thousands of mutations in the binding domains of multiple SARS-CoV-2 variants,” Nature reported. “They also catalogued mutations in the binding domain on dozens of SARS-CoV-2-like coronaviruses that belong to a group called the sarbecoviruses. Finally, they assessed how all these mutations affect the 12 antibodies’ ability to stick to the binding domain.”

William Schaffner, MD

William Schaffner, MD (above), Professor of Preventive Medicine in the Department of Health Policy as well as Professor of Medicine in the Division of Infectious Diseases at the Vanderbilt University School of Medicine in Nashville, believes that “people who test positive for SARS-CoV-2 and who are at risk of progressing to severe disease—including those who are over the age of 65 years and those who have weakened immune systems—should talk with a doctor about receiving monoclonal antibody treatment,” Medical News Today reported. “[The monoclonal antibody treatment is] designed to prevent the evolution of the infection from a mild infection into a serious one,” he noted. “In other words, you’ve just [contracted the virus], but we can now give you a medication that will help prevent [you] being hospitalized and getting seriously ill.” (Photo copyright: Vanderbilt University.)

Earlier Antibody Treatment Receives an EUA from the FDA

Another antibody studied by the researchers, S309, has already led to a monoclonal antibody therapy authorized for use in the US. On May 26, the FDA issued an emergency use authorization (EUA) for sotrovimab, a therapy developed by GlaxoSmithKline (NYSE:GSK) and Vir Biotechnology, according to SciTechDaily.

In issuing the EUA for sotrovimab, the FDA cited “an interim analysis from a phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in 583 non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. Of these patients, 291 received sotrovimab and 292 received a placebo within five days of onset of COVID-19 symptoms.”

Among these patients, 21 in the placebo group were hospitalized or died compared with three who received the therapy, an 85% reduction.

“While preventive measures, including vaccines, can reduce the total number of cases, sotrovimab is an important treatment option for those who become ill with COVID-19 and are at high risk—allowing them to avoid hospitalization or worse,” stated Adrienne E. Shapiro, MD, PhD, of the Fred Hutchinson Cancer Research Center in a GSK news release. Shapiro was an investigator in the clinical trial.

The EUA allows use of sotrovimab in patients who have tested positive for SARS-CoV-2, have mild-to-moderate symptoms, and “who are at high risk for progression to severe COVID-19, including hospitalization or death. This includes, for example, individuals who are 65 years of age and older or individuals who have certain medical conditions.” It is not authorized for patients who are hospitalized or for those who require oxygen therapy.

The therapy was originally known as VIR-7831. The companies say they have developed a similar treatment, VIR-7832, with modifications designed to enhance T cell function against the disease.

In “The Dual Function Monoclonal Antibodies VIR-7831 and VIR-7832 Demonstrate Potent In Vitro and In Vivo Activity Against SARS-CoV-2,” published on bioRxiv, researchers from Vir Biotechnology wrote that the S309 antibody was isolated from a survivor of the earlier outbreak of SARS-CoV-1.

The antibody, they wrote, targets a region of the SARS-CoV-1 spike protein that is “highly conserved” among sarbecoviruses. Clinical laboratory testing, they wrote, also indicated that the therapy was likely to be effective against known SARS-CoV-2 variants.

“Our distinctive scientific approach has led to a single monoclonal antibody that, based on an interim analysis, resulted in an 85% reduction in all-cause hospitalizations or death, and has demonstrated, in vitro, that it retains activity against all known variants of concern, including the emerging variant from India,” stated Vir Biotechnology CEO George Scangos, PhD, in the GSK news release. “I believe that sotrovimab is a critical new treatment option in the fight against the current pandemic and potentially for future coronavirus outbreaks, as well.”

Pathologists and clinical laboratory managers working with rapid molecular tests and antibody tests for COVID-19 will want to monitor the development of monoclonal antibody treatments, as well as further research studies that focus on these specific antibodies.

Stephen Beale

Related Information:

Reduced Sensitivity of SARS-CoV-2 Variant Delta to Antibody Neutralization

SARS-CoV-2 RBD Antibodies That Maximize Breadth and Resistance to Escape

This ‘Super Antibody’ for COVID Fights Off Multiple Coronaviruses

Scientist at Berkeley Lab Played a Hand in “Inescapable” COVID-19 Antibody

Decades-Old SARS Virus Infection Triggers Potent Response to COVID Vaccines

The Dual Function Monoclonal Antibodies VIR-7831 and VIR-7832 Demonstrate Potent In Vitro and In Vivo Activity Against SARS-CoV-2

How Studies of Coronavirus Immunity Can Inform Better Vaccines, Treatments

Scientists Discover Antibodies That May Neutralize a Range of SARS-CoV-2 Variants

Proof-of-Concept Study at University of Colorado Boulder Shows Dynamic Tattoos Can Help Detect and Track Health Issues

If tattoos can accurately be used in the diagnostic process, might clinical laboratories soon offer these types of diagnostic tattoos at their patient service centers?

Could color-changing tattoos help diagnose illnesses? Researchers at the ATLAS Institute at the University of Colorado Boulder think so. They are working on prototypes of permanent tattoos that can detect chemical changes in the body and smart tattoo ink that would take the concept of wearable medical devices to a whole new level.

Called “dynamic” or “smart” tattoos, these color-changing tattoos have a biomedical purpose. They alert individuals to potential health issues due to changes in the biochemistry in their body. The technology has already been used in animal studies to detect sodium, glucose, electrolytes, and pH levels. Pathologists and clinical lab manager will recognize the value of a relatively non-invasive way to measure and track changes in these types of biomarkers.

The ATLAS Institute published its findings in ACS Nano, a publication of the American Chemical Society, titled, “Solar Freckles: Long-Term Photochromic Tattoos for Intradermal Ultraviolet Radiometry.”

“We developed a photochromic tattoo that serves as an intradermal ultraviolet (UV) radiometer that provides naked-eye feedback about UV exposure in real time. These small tattoos, or ‘solar freckles’, comprise dermally implanted colorimetric UV sensors in the form of nano encapsulated leuco dyes that become more blue in color with increasing UV irradiance,” the ATLAS scientists wrote.

Studies analyzing the efficacy of dynamic tattoos have provided strong evidence that they can be engineered to change color and sense and convey medical information. This field is called “dynamic tattoos” and in recent years various proof-of-concept studies have demonstrated that tattoos can be used to “pick up changes in sodium, glucose, electrolytes or pH levels in animal models,” Labroots reported.

“We demonstrate the tattoos’ functionality for both quantitative and naked-eye UV sensing in porcine skin ex vivo, as well as in human skin in vivo. Solar freckles offer an alternative and complementary approach to self-monitoring UV exposure for the sake of skin cancer prevention,” the researchers explained in their ACS Nano article.

“Activated solar freckles provide a visual reminder to protect the skin, and their color disappears rapidly upon removal of UV exposure or application of topical sunscreen. The sensors are implanted in a minimally invasive procedure that lasts only a few seconds yet remain functional for months to years,” they added.

“These semipermanent tattoos provide an early proof-of-concept for long-term intradermal sensing nanomaterials that provide users with biomedically relevant information in the form of an observable color change,” the ATLAS researchers concluded.

Nanotechnology Gives Dynamic Tattoos Functionality

“When you think about what a tattoo is, it’s just a bunch of particles that sit in your skin,” Carson Bruns, PhD, Assistant Professor, Laboratory for Emergent Nanomaterials, ATLAS Institute, Mechanical Engineering, told Technology.org. “Our thought is: What if we use nanotechnology to give these particles some function?”

The invisible tattoos Bruns and the ATLAS team created turn blue in the presence of harmful levels of ultraviolet radiation to inform wearers that their skin needs protection and to apply or reapply sunscreen.

Carson Bruns, PhD

“I have always been interested in both art and science. My favorite type of art is tattooing and my favorite type of science is nanotechnology,” Carson Bruns, PhD (above), Assistant Professor, Mechanical Engineering, ATLAS Institute, told Inked. “When I had an opportunity to start a new research program, I thought it would be really fun and interesting to try and put the two together.” Might innovative medical laboratories one day operate “tattoo parlors” in their patient service centers to provide patients with tattoos that monitor key biometrics? (Photo copyright: Inked.)

The tattoo ink used for these tattoos contains a UV-activated dye inside of a plastic nano capsule that is less than a thousandth of a millimeter in size, or several sizes smaller than the width of a human hair. The capsules protect the dyes from wear and tear while allowing them to sense and respond to biochemical changes in the body. These tattoos are implanted into the skin using tattoo machines, much like getting a regular tattoo.

“I call them solar freckles because they’re like invisible freckles that are powered by sunshine,” Bruns told Inked, adding, “Millions of cases of preventable skin cancer are treated every year. I hope that the UV-sensitive tattoo will help us reduce the number of those cases by reminding people when their skin is exposed to unsafe levels of UV light.”

Dynamic Tattoos May Help People Lead Healthier Lives

One downside to these tattoos is that they only last a few months before they begin to degrade, requiring the wearer to get a “booster” tattoo.

The researchers hope that someday similar tattoo technologies will be applied to a wide variety of preventative and diagnostic applications. The goal is to enable people to detect health issues and allow them to lead healthier lives. 

“We want to make tattoos that will allow you to, for example, sense things that you can’t currently sense,” Bruns told Inked. “Sometimes I joke that we want to make tattoos that give you superpowers.”

The ATLAS scientists imagine a future where tattoos can detect things like blood alcohol levels or high/low blood sugar levels or other changes in a person’s biochemistry.

“More generally, I hope that smart tattoos will help people stay healthy and more informed about their body, while also giving people new ways to express themselves creatively,” Bruns said.

Using Dynamic Tattoo to Detect Cancer

In 2018, a team of biologists created a tattoo comprised of engineered skin cells and an implantable sensor which could detect elevated blood calcium levels that are present in many types of cancers. These cancer-detecting tattoos were tested on living mice and would darken to notify researchers of potential problems.

Scientists at the Department of Biosystems Science and Engineering at the Swiss Federal Institute of Technology Zurich (ETHZ), Switzerland, developed a biomedical tattoo that uses bio sensitive ink and changes color based on variations in the body’s interstitial fluid. It recognizes four widespread cancers:

  • breast,
  • colon,
  • lung, and
  • prostate.

“Nowadays, people generally go to the doctor only when the tumor begins to cause problems. Unfortunately, by that point it is often too late,” Martin Fussenegger, PhD, Professor of Biotechnology and Bioengineering at the Department of Biosystems Science and Engineering (D-​BSSE) of the ETH Zurich in Basel as well as at the University of Basel, told Medical News Today.

“For example, if breast cancer is detected early, the chance of recovery is 98%,” he continued. “However, if the tumor is diagnosed too late, only one in four women has a good chance of recovery.”

Fussenegger and his team hope their specialized biomedical tattoo may help detect the presence of cancer cells early and significantly improve patient outcomes. They published the results of their research in the journal Science Translational Medicine, titled, “Synthetic Biology-Based Cellular Biomedical Tattoo for Detection of Hypercalcemia Associated with Cancer.”

Though it appears that dynamic tattoos may be a functional and decorative way to track health, rigorous research and safety testing on human subjects will be required before clinical laboratories can set up diagnostic tattoo parlors in their offices.

Nevertheless, this concept demonstrates how different technologies under development may provide clinical laboratories with innovative and unusual diagnostic tools in the future.

JP Schlingman

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Synthetic Biology-based Cellular Biomedical Tattoo for Detection of Hypercalcemia Associated with Cancer

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