Study of the 50 Omicron variants could lead to new approaches to clinical laboratory testing and medical treatments for long COVID
Patients infected with SARS-CoV-2 can usually expect the COVID-19 illness to subside within a couple of weeks. However, one Dutch patient remained infected with the coronavirus for 612 days and fought more than 50 mutations (aka, variants) before dying late last year of complications due to pre-existing conditions. This extreme case has given doctors, virologists, microbiologists, and clinical laboratories new insights into how the SARS-CoV-2 virus mutates and may lead to new treatments for long COVID.
The medication the patient was taking for his pre-existing conditions may have contributed to his body being unable to produce antibodies in response to three shots of the Moderna mRNA COVID vaccine he received.
Magda Vergouwe, MD, PhD candidate at the Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, who lead a study into the patient, theorized that some of the medications the patient was on for his pre-existing conditions could have destroyed healthy cells alongside the abnormal cancer-causing B cells the drugs were meant to target.
“This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals,” the researchers said prior to presenting their report about the case at a meeting of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in Barcelona, Spain, Time reported. “We emphasize the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections.”
“Chronic infections and viral evolution [are] commonly described in [the] literature, and there are other cases of immunocompromised patients who have had [COVID] infections for hundreds of days,” Magda Vergouwe, MD, PhD candidate (above), Center for Experimental and Molecular Medicine at Amsterdam UMC, told Scientific American. “But this is unique due to the extreme length of the infection … and with the virus staying in his body for so long, it was possible for mutations to just develop and develop and develop.” Microbiologists, virologists, and clinical laboratories involved in testing patients with long COVID may want to follow this story. (Photo copyright: LinkedIn.)
Risks to Immunocompromised Patients
Pre-existing conditions increase the risk factor for COVID-19 infections. A 2021 study published in the Journal of the American Board of Family Medicine (JABFM) titled, “Prevalence of Pre-existing Conditions among Community Health Center Patients with COVID-19,” found that about 61% of that study’s test group had a pre-existing condition prior to the outbreak of the COVID-19 pandemic.
When the Dutch man was admitted to Amsterdam UMC with common and serious COVID-19 symptoms, such as shortness of breath, a cough, and low blood oxygen levels, he was prescribed sotrovimab (a monoclonal antibody) along with other COVID treatments.
About a month after being admitted his COVID-19 symptoms decreased, so he was first discharged to a rehab facility and then finally to his home. However, he continued to test positive for the coronavirus and developed other infections that may have been complicated by the persistent case of COVID-19.
The Amsterdam UMC doctors emphasized that the man ultimately succumbed to his pre-existing conditions and not necessarily COVID-19.
“It’s important to note that in the end he did not die from his COVID-19,” Vergouwe told Scientific American. “But he did keep it with him for a very long period of time until then, and this is why we made sure to sample [the virus in his body] as much as we could.”
One in Five Adults Develop Long COVID
Long COVID does not necessarily indicate an active infection. However, in as many as one in five US adults COVID symptoms persist after the acute phase of the infection is over, according to a study published recently in JAMA Network Open titled, “Epidemiologic Features of Recovery from SARS-CoV-2 Infection.”
“In this cohort study, more than one in five adults did not recover within three months of SARS-CoV-2 infection. Recovery within three months was less likely in women and those with pre-existing cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave,” the JAMA authors wrote.
The origins of long COVID are not entirely clear, but according to the National Institutes of Health (NIH) it can develop when a patient is unable to sufficiently rest while battling off the initial virus. According to Vergouwe, the SARS-CoV-2 genome will always grow quicker when found in a patient with a compromised immune system.
Unique COVID-19 Mutations
More than 50 new mutations of the original Omicron variant were identified in the Dutch patient. According to Vergouwe, “while that number can sound shocking, mutations to the SARS-CoV-2 genome are expected to evolve more quickly in those who are immunocompromised (the average mutation rate of the virus is estimated to be two mutations per person per month),” Scientific American reported. “What does make these mutations unusual, she noted, is how their features differed vastly from mutations observed in other people with COVID. [Vergouwe] hypothesizes that the exceptional length of the individual’s infection, and his pre-existing conditions, allowed the virus to evolve extensively and uniquely.”
COVID-19 appears to be here to stay, and most clinical laboratory managers and pathologists understand why. As physicians continue to learn about the SARS-CoV-2 coronavirus, this is another example of how the knowledge about SARS-CoV-2 is growing as different individuals are infected with different variants of the virus.
New guidelines also advise people to limit their vitamin D supplementation to recommended daily doses
Clinical laboratories may eventually receive fewer doctors’ orders for vitamin D testing thanks to new guidelines released by the Endocrine Society. The new Clinical Practice Guideline advises against “unnecessary testing for vitamin D levels.” It also urges healthy people, and those 75-years of age or younger, to avoid taking the vitamin at levels above the daily recommended amounts, according to a news release.
Even though the Endocrine Society does recommend vitamin D supplements for certain groups, it advises individuals to hold off on routine testing. That’s because there appears to be uncertainty among ordering clinicians about what to do for patients based on their vitamin D test results.
“When clinicians measure vitamin D, they’re forced to decide what to do about it. That’s where questions about the levels come in. And that’s a big problem. So, what this panel is saying is ‘Don’t screen,’” Clifford Rosen, MD, Director of Clinical and Translational Research and Senior Scientist, Maine Medical Center Research Institute at the University of Maine, told Medscape Medical News.
“We have no data that there’s anything about screening that allows us to improve quality of life. Screening is probably not worthwhile in any age group,” he added.
“This guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them,” the author of the Endocrine Society guideline, Anastassios G. Pittas, MD (above), Professor of Medicine at Tufts University School of Medicine in Boston, told Medscape Medical News. This new guideline could result in doctors ordering fewer vitamin D tests from clinical laboratories. (Photo copyright: Tufts University.)
Vitamin D Screening Not Recommended for Certain Groups
The Endocrine Society’s new clinical guidelines advise healthy adults under 75 years of age to refrain from taking vitamin D supplements that exceed US Institute of Medicine—now the National Academy of Medicine (NAM)—recommendations.
Additionally, these updated guidelines:
Recommend vitamin D supplements at levels above NAM recommendations to help lower risks faced by children 18 years and younger, adults 75 and older, pregnant women, and people with prediabetes.
Suggest daily, lower-dose vitamin D (instead of non-daily, higher-dose of the vitamin) for people 50 years and older who have “indications for vitamin D supplementation or treatment.”
Advise “against routine testing for 25-hydroxyvitamin D [aka, calcifediol] levels” in all the above groups “since outcome-specific benefits based on these levels have not been identified. This includes 25-hyrdoxyvitamin D screening in people with dark complexion or obesity.”
One exception to the guideline applies to people with already established osteoporosis, according to the guideline’s author endocrinologist Anastassios G. Pittas, MD, Chief of Endocrinology, Diabetes and Metabolism; Co-Director, Tuft’s Diabetes and Lipid Center; and Professor of Medicine at Tufts University School of Medicine in Boston.
Vitamin D’s Link to Disease Studied
During a panel discussion at the Endocrine Society’s annual meeting, members acknowledged that many studies have shown relationships between serum concentrations of 25-hydroxy vitamin D (25(OH)D) and physical disorders including those of musculoskeletal, metabolic, and cardiovascular systems. Still, they questioned the link of vitamin D supplementation and testing with disease prevention.
“There is paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases. … What we really need are large-scale clinical trials and biomarkers so we can predict disease outcome before it happens,” said Panel Chair Marie Demay, MD, Endocrinologist, Massachusetts General Hospital, and Professor of Medicine, Harvard Medical School, Boston, Medscape Medical News reported.
Meanwhile, in their Journal of Clinical Endocrinology and Metabolism paper, the researchers note that use of supplements (1,000 IU or more per day) increased from 0.3% to 18.2%, according to the National Health and Nutrition Examination Survey (NHANES) conducted by the National Center for Health Statistics (NCHS), CDC, for the years 1999-2000 and 2013-2014.
“The use of 25(OH)D testing in clinical practice has also been increasing; however, the cost effectiveness of widespread testing has been questioned, especially given the uncertainty surrounding the optimal level of 25(OH)D required to prevent disease,” the authors wrote.
“Thus, the panel suggests against routine 25(OH)D testing in all populations considered,” the researchers stated at the Endocrine Society annual meeting.
Other Groups Weigh-in on Vitamin D Testing
Pathologists and medical laboratory leaders may recall the explosion in vitamin D testing starting about 20 years ago. Vitamin D testing reimbursed by Medicare Part B “increased 83-fold” during the years 2000 to 2010, according to data cited in an analysis by the American Academy of Family Physicians (AAFP).
Also, the US Preventive Services Task Force (USPSTF) said in a statement that there is not enough information to “recommend for or against” testing for vitamin D deficiency.
“No organization recommends population-based screening for vitamin D deficiency, and the American Society for Clinical Pathology recommends against it,” the USPSTF noted.
Clinical Laboratories Can Get the Word Out
The vitamin D debate has been going on for a while. And the latest guidance from the Endocrine Society may cause physicians and patients to stop ordering vitamin D tests as part of annual physicals or in routine screenings.
Medical laboratories can provide value by ensuring physicians and patients have the latest information about vitamin D test orders, reports, and interpretation.
Infection control teams and clinical laboratory managers may want to look at this new product designed to improve the diagnosis and treatment of sepsis
Accurate and fast diagnosis of sepsis for patients arriving in emergency departments is the goal of a new product that was just cleared by the federal Food and Drug Administration (FDA). It is also the newest example of how artificial intelligence (AI) continues to find its way into pathology and clinical laboratory medicine.
Sepsis is one of the deadliest killers in US hospitals. That is why there is interest in the recent action by the FDA to grant marketing authorization for an AI-powered sepsis detection software through the agency’s De Novo Classification Request. The DNCR “provides a marketing pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device,” the FDA’s website states.
Unlike a single analyte assay that is run in a clinical laboratory, Prenosis’ AI/ML software uses 22 diagnostic and predictive parameters, along with ML algorithms, to analyze data and produce a clinically actionable answer on sepsis.
It is important for clinical laboratory managers and pathologists to recognize that this diagnostic approach to sepsis brings together a number of data points commonly found in a patient’s electronic health record (EHR), some of which the lab generated and others the lab did not generate.
“Sepsis is a serious and sometimes deadly complication. Technologies developed to help prevent this condition have the potential to provide a significant benefit to patients,” said Jeff Shuren, MD, JD, Director of the FDA’s Center for Devices and Radiological Health, in a statement. “The FDA’s authorization of the Prenosis Sepsis ImmunoScore software establishes specific premarket and post-market requirements for this device type.” Clinical laboratory EHRs contain some of the data points Prenosis’ diagnostic software uses. (Photo copyright: US Food and Drug Administration.)
How it Works
To assist doctors diagnose sepsis, the ImmunoScore software is first integrated into the patient’s hospital EHR. From there, it leverages 22 parameters including:
White blood cell count to produce a score that informs caregivers of the patient’s risk for sepsis within 24 hours, MedTech Dive reported.
Instead of requiring a doctor or nurse to look at each parameter separately, the SaMD tool uses AI “to evaluate all those markers at once”, CNBC noted. It then produces a risk score and four discrete risk stratification categories (low, medium, high, and very high) which correlate to “a patient’s risk of deterioration” represented by:
By sharing these details—a number from one to 100 for each of the 22 diagnostic and predictive parameters—Sepsis ImmunoScore helps doctors determine which will likely contribute most to the patient’s risk for developing sepsis, MedTech Dive reported.
“A lot of clinicians don’t trust AI products for multiple reasons. We are trying very hard to counter that skepticism by making a tool that was validated by the FDA first, and then the second piece is we’re not trying to replace the clinician,” Bobby Reddy Jr., PhD, Prenosis co-founder and CEO, told MedTech Dive.
Big Biobank and Blood Sample Data
Prenosis, which says its goal is the “enabling [of] precision medicine in acute care” developed Sepsis ImmunoScore using the company’s own biobank and a dataset of more than 100,000 blood samples from more than 25,000 patients.
AI algorithms drew on this biological/clinical dataset—the largest in the world for acute care patients suspected of having serious infections, according to Prenosis—to “elucidate patterns in rapid immune response.”
“It does not work without data, and the data started at Carle,” said critical care specialist Karen White, MD, PhD, Carle Foundation Hospital, St. Louis, MO, in the news release. “The project involved a large number of physicians, research staff, and internal medicine residents at Carle who helped recruit patients, collect data, and samples,” she said.
Opportunity for Clinical Laboratories
Sepsis is a life-threatening condition based on an “extreme response to an infection” that affects nearly 1.7 million adults in the US each year and is responsible for 350,000 deaths, according to US Centers for Disease Control and Prevention (CDC) data.
A non-invasive diagnostic tool like Sepsis ImmunoScore will be a boon to emergency physicians and the patients they treat. Now that the FDA has authorized the SaMD diagnostic tool to go to market, it may not be long before physicians can use the information it produces to save lives.
Clinical laboratory managers inspired by the development of Sepsis ImmunoScore may want to look for similar ways they can take certain lab test results and combine them with other data in an EHR to create intelligence that physicians can use to better treat their patients. The way forward in laboratory medicine will be combining lab test results with other relevant sets of data to create clinically actionable intelligence for physicians, patients, and payers.
Findings could lead to new biomarkers clinical laboratories would use for identifying cancer in patients and monitoring treatments
As DNA “dark matter” (the DNA sequences between genes) continues to be studied, researchers are learning that so-called “junk DNA” (non-functional DNA) may influence multiple health conditions and diseases including cancer. This will be of interest to pathologists and clinical laboratories engaged in cancer diagnosis and may lead to new non-invasive liquid biopsy methods for identifying cancer in blood draws.
This technique could enable non-invasive monitoring of cancer treatment and cancer diagnosis, Technology Networks noted.
“Our study shows that ARTEMIS can reveal genomewide repeat landscapes that reflect dramatic underlying changes in human cancers,” said study co-leader Akshaya Annapragada (above), an MD/PhD student at the Johns Hopkins University School of Medicine, in a news release. “By illuminating the so-called ‘dark genome,’ the work offers unique insights into the cancer genome and provides a proof-of-concept for the utility of genomewide repeat landscapes as tissue and blood-based biomarkers for cancer detection, characterization, and monitoring.” Clinical laboratories may soon have new biomarkers for the detection of cancer. (Photo copyright: Johns Hopkins University.)
Detecting Early Lung, Liver Cancer
Artemis is a Greek word meaning “hunting goddess.” For the Johns Hopkins researchers, ARTEMIS also describes a technique “to analyze junk DNA found in tumors” and which float in the bloodstream, Financial Times explained.
“It’s like a grand unveiling of what’s behind the curtain,” said geneticist Victor Velculescu, MD, PhD, Professor of Oncology and co-director of the Cancer Genetics and Epigenetics Program at Johns Hopkins Kimmel Cancer Center, in the news release.
“Until ARTEMIS, this dark matter of the genome was essentially ignored, but now we’re seeing that these repeats are not occurring randomly,” he added. “They end up being clustered around genes that are altered in cancer in a variety of different ways, providing the first glimpse that these sequences may be key to tumor development.”
ARTEMIS could “lead to new therapies, new diagnostics, and new screening approaches for cancer,” Velculescu noted.
Repeats of DNA Sequences Tough to Study
For some time technical limitations have hindered analysis of repetitive genomic sequences by scientists.
“Genetic changes in repetitive sequences are a hallmark of cancer and other diseases, but characterizing these has been challenging using standard sequencing approaches,” the study authors wrote in their Science Translational Medicine paper.
“We developed a de novok-mer (short sequences of DNA)-finding approach called ARTEMIS to identify repeat elements from whole-genome sequencing,” the researchers wrote.
The scientists put ARTEMIS to the test in laboratory experiments.
The first analysis involved 1,280 types of repeating genetic elements “in both normal and tumor tissues from 525 cancer patients” who participated in the Pan-Cancer Analysis of Whole Genomes (PCAWG), according to Technology Networks, which noted these findings:
A median of 807 altered elements were found in each tumor.
About two-thirds (820) had not “previously been found altered in human cancer.”
Second, the researchers explored “genomewide repeat element changes that were predictive of cancer,” by using machine learning to give each sample an ARTEMIS score, according to the Johns Hopkins news release.
The scoring detected “525 PCAWG participants’ tumors from the healthy tissues with a high performance” overall Area Under the Curve (AUC) score of 0.96 (perfect score being 1.0) “across all cancer types analyzed,” the Johns Hopkins’ release states.
Liquid Biopsy Deployed
The scientists then used liquid biopsies to determine ARTEMIS’ ability to noninvasively diagnose cancer. Researchers used blood samples from:
ARTEMIS classified patients with lung cancer with an AUC of 0.82.
ARTEMIS detected people with liver cancer, as compared to others with cirrhosis or viral hepatitis, with a score of AUC 0.87.
Finally, the scientists used their “ARTEMIS blood test” to find the origin of tumors in patients with cancer. They reported their technique was 78% accurate in discovering tumor tissue sources among 12 tumor types.
“These analyses reveal widespread changes in repeat landscapes of human cancers and provide an approach for their detection and characterization that could benefit early detection and disease monitoring of patients with cancer,” the researchers wrote in Science Translational Medicine.
Large Clinical Trials Planned
Velculescu said more research is planned, including larger clinical trials.
“While still at an early stage, this research demonstrates how some cancers could be diagnosed earlier by detecting tumor-specific changes in cells collected from blood samples,” Hattie Brooks, PhD, Research Information Manager, Cancer Research UK (CRUK), told Financial Times.
Should ARTEMIS prove to be a viable, non-invasive blood test for cancer, it could provide pathologists and clinical laboratories with new biomarkers and the opportunity to work with oncologists to promptly diagnosis cancer and monitor patients’ response to treatment.
Findings could lead to clinical laboratory tests that help physicians identify microbes lacking in the microbiomes of their Parkinson patients
Microbiologists and clinical laboratory scientists know that gut microbiome can be involved in the development of Parkinson’s disease, a progressive neurological disorder that affects the nervous system due to damage caused to nerve cells in the brain. There is no cure for the illness. But a new treatment developed by researchers at the VIB Center for Inflammation Research at the University of Ghent in Belgium, may help to alleviate the symptoms.
During a clinical trial, VIB Center for Inflammation Research (VIB-IRC) scientists discovered that fecal microbiota transplantation (FMT), also known as a stool transplant, can improve motor skills in some Parkinson’s patients, according to Neuroscience News.
Parkinson’s disease (PD) develops when a protein called alpha-synuclein misfolds and forms into bundled clusters damaging nerve cells in the brain that produce dopamine. These formations, which are believed to appear in the gastrointestinal wall in the early stages of PD, then reach the brain via the vagus nerve leading to typical PD symptoms in patients.
“Our study provides promising hints that FMT can be a valuable new treatment for Parkinson’s disease,” Roosmarijn Vandenbroucke, PhD (above), Principal Investigator, VIB-UGent Center for Inflammation Research and full professor, UGent Department of Biomedical molecular biology, Faculty of Sciences, told Neuroscience News. “More research is needed, but it offers a potentially safe, effective, and cost-effective way to improve symptoms and quality of life for millions of people with Parkinson’s disease worldwide.” Clinical laboratories will likely be involved in identifying the best microbes for the FMT treatments. (Photo copyright: University of Ghent.)
Correlation between Gut Microbiome and Neurogenerative Disease
To perform their clinical study—referred to as GUT-PARFECT—the IRC researchers first recruited patients with early-stage PD and healthy donors who provided stool samples to the Ghent Stool Bank. The PD patients received the healthy stool via a tube inserted into the nose which led directly into the small intestine.
The FMT procedures were performed on 46 patients with PD between December 2020 and December 2021. The participants in this group ranged in ages from 50 to 65. There were 24 PD patients in the placebo group, and a total of 22 donors provided the healthy stool. Clinical evaluations were performed at baseline, three, six, and 12 months.
After 12 months, the group that received the transplants showed a reduction in symptoms compared to the placebo group. Their motor score on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) improved by a mean of 5.8 points. The improvement registered on the same scale for the placebo group was 2.7 points.
Developed in the 1980s, the MDS-UPDRS is a scale utilized to evaluate various aspects of PD by measuring patient responses via a questionnaire rating several issues (such as cognitive impairment, apathy, depression, and anxiousness) common in PD patients from normal to severe. It is divided into four parts:
Part I: Non-motor experiences of daily living.
Part II: Motor experiences of daily living.
Part III: Motor examination.
Part IV: Motor complications.
During the final six months of the research, the improvement in motor symptoms became even greater. To the VIB-IRC researchers this implied that an FMT may have long-lasting effects on PD patients. The FMT study group also experienced less constipation, a condition that can be bothersome for some PD patients.
“Our results are really encouraging!” said the study’s first author, Arnout Bruggeman, MD, PhD student, VIB-UGent Center for Inflammation Research, in a UGent News release. “After twelve months, participants who received the healthy donor stool transplant showed a significant improvement in their motor score, the most important measure for Parkinson’s symptoms.”
Findings Could Lead to Other Targeted Therapies for PD
The VIB-IRC researchers believe there is a correlation between the gut microbiome and Parkinson’s disease.
“Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages,” the IRC researchers wrote in eClinicalMedicine.
“Our next step is to obtain funding to determine which bacteria have a positive influence. This could lead to the development of a ‘bacterial pill’ or other targeted therapy that could replace FMT in the future,” Debby Laukens, PhD, Associate Professor, Ghent University, told Neuroscience News.
According to the Parkinson’s Foundation website, nearly one million people in the US live with PD. It is second only to Alzheimer’s disease in the category of neurodegenerative diseases.
More research and studies are needed before the VIB-IRC’s stool transplant treatment can be used in clinical care. As researchers learn more about which specific strains of bacteria are doing the beneficial work in PD patients, that data could eventually lead to clinical laboratory tests performed to help physicians identify which microbes are lacking in the microbiomes of their PD patients, and if fecal transplants could help those patients.
Accurate blood-based clinical laboratory testing for cancer promises to encourage more people to undergo early screening for deadly diseases
One holy grail in diagnostics is to develop less-invasive specimen types when screening or testing for different cancers. This is the motivation behind the creation of a new assay for colorectal (colon) cancer that uses a blood sample and that could be offered by clinical laboratories. The data on this assay and its performance was featured in a recent issue of the New England Journal of Medicine(NEJM).
The company developing this new test recognized that more than 50,000 people will die in 2024 from colon cancer, according to the American Cancer Society. That’s primarily because people do not like colonoscopies even though the procedure can detect cancer in its early stages. Similarly, patients tend to find collecting their own fecal samples for colon cancer screening tests to be unpleasant.
But the clinical laboratory blood test for cancer screening developed by Guardant Health may make diagnosing the deadly disease less invasive and save lives. The test “detects 83% of people with colorectal cancer with specificity of 90%,” a company press release noted.
“Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality,” the study authors wrote in the NEJM.
As noted above, this is the latest example of test developers working to develop clinical laboratory tests that are less invasive for patients, while equaling or exceeding the sensitivity and specificity of existing diagnostic assays for certain health conditions.
“I do think having a blood draw versus undergoing an invasive test will reach more people, My hope is that with more tools we can reach more people,” Barbara H. Jung, MD (above), President of the American Gastroenterological Association, told NPR. Clinical laboratory blood tests for cancer may encourage people who do not like colonoscopies to get regular screening. (Photo copyright: American Gastroenterology Association.)
Developing the Shield Blood Test
Colorectal cancer is the “third most common cancer among men and women in the US,” according to the American Gastrological Association (AGA). And yet, millions of people do not get regular screening for the disease.
To prove their Shield blood test, Guardant Health, a precision oncology company based in Redwood City, Calif., enrolled more than 20,000 patients between the ages of 45-84 from across the US in a prospective, multi-site registrational study called ECLIPSE (Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Episode).
“We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions,” the study authors wrote in the NEJM.
In March, Guardant completed clinical trials of its Shield blood test for detecting colorectal cancer (CRC) in men and women. According to the company press release, the test demonstrated:
83% sensitivity in detecting individuals with CRC.
88% sensitivity in detecting pathology-confirmed Stages I-III.
Additionally, the Shield test showed sensitivity by stage of:
65% for pathology-confirmed Stage I,
55% for clinical Stage I,
100% for Stage II, and
100% for Stage III.
“The results of the study are a promising step toward developing more convenient tools to detect colorectal cancer early while it is more easily treated,” said molecular biologist and gastroenterologist William M. Grady, MD, Medical Director, Gastrointestinal Cancer Prevention Program at Fred Hutchinson Cancer Center and corresponding author of the ECLIPSE study in the press release. “The test, which has an accuracy rate for colon cancer detection similar to stool tests used for early detection of cancer, could offer an alternative for patients who may otherwise decline current screening options.”
Are Colonoscopies Still Needed?
“More than three out of four Americans who die from colorectal cancer are not up to date with their recommended screening, highlighting the need for a more convenient and less invasive screening method that can overcome barriers associated with traditional options,” Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, said in the Guardant press release.
Barbara H. Jung, MD, President of the American Gastroenterological Association, says that even if Guardant’s Shield test makes it to the public the “dreaded colonoscopy” will still be needed because the procedure is used to locate and test polyps. “And when you find those you can also remove them, which in turn prevents the cancer from forming,” she told NPR.
There is hope that less invasive clinical laboratory testing will encourage more individuals to get screened for cancer earlier and regularly, and that the shift will result in a reduction in cancer rates.
“Colorectal cancer is highly treatable if caught in the early stages,” said Chris Evans, President of the Colon Cancer Coalition, in the Guardant press release.
Guardant Health’s ECLIPSE study is a prime example of the push clinical laboratory test developers are making to create user-friendly test options that make it easier for patients to follow through with regular screening for early detection of diseases. It echoes a larger effort in the medical community to think outside the box and come up with creative solutions to reach wider audiences in the name of prevention.
