Findings could lead to deeper understanding of why we age, and to medical laboratory tests and treatments to slow or even reverse aging
Can humans control aging by keeping their genes long and balanced? Researchers at Northwestern University in Evanston, Illinois, believe it may be possible. They have unveiled a “previously unknown mechanism” behind aging that could lead to medical interventions to slow or even reverse aging, according to a Northwestern news release.
Should additional studies validate these early findings, this line of testing may become a new service clinical laboratories could offer to referring physicians and patients. It would expand the test menu with assays that deliver value in diagnosing the aging state of a patient, and which identify the parts of the transcriptome that are undergoing the most alterations that reduce lifespan.
It may also provide insights into how treatments and therapies could be implemented by physicians to address aging.
“I find it very elegant that a single, relatively concise principle seems to account for nearly all of the changes in activity of genes that happen in animals as they change,” Thomas Stoeger, PhD, postdoctoral scholar in the Amaral Lab who led the study, told GEN. Clinical laboratories involved in omics research may soon have new anti-aging diagnostic tests to perform. (Photo copyright: Amaral Lab.)
Possible ‘New Instrument’ for Biological Testing
Researchers found clues to aging in the length of genes. A gene transcript length reveals “molecular-level changes” during aging: longer genes relate to longer lifespans and shorter genes suggest shorter lives, GEN summarized.
The phenomenon the researchers uncovered—which they dubbed transcriptome imbalance—was “near universal” in the tissues they analyzed (blood, muscle, bone, and organs) from both humans and animals, Northwestern said.
According to the National Human Genome Research Institute fact sheet, a transcriptome is “a collection of all the gene readouts (aka, transcript) present in a cell” shedding light on gene activity or expression.
The Northwestern study suggests “systems-level” changes are responsible for aging—a different view than traditional biology’s approach to analyzing the effects of single genes.
“We have been primarily focusing on a small number of genes, thinking that a few genes would explain disease,” said Luis Amaral, PhD, Senior Author of the Study and Professor of Chemical and Biological Engineering at Northwestern, in the news release.
“So, maybe we were not focused on the right thing before. Now that we have this new understanding, it’s like having a new instrument. It’s like Galileo with a telescope, looking at space. Looking at gene activity through this new lens will enable us to see biological phenomena differently,” Amaral added.
In their Nature Aging paper, Amaral and his colleagues wrote, “We hypothesize that aging is associated with a phenomenon that affects the transcriptome in a subtle but global manner that goes unnoticed when focusing on the changes in expression of individual genes.
“We show that transcript length alone explains most transcriptional changes observed with aging in mice and humans,” they continued.
In tissues studied, older animals’ long transcripts were not as “abundant” as short transcripts, creating “imbalance.”
“Imbalance” likely prohibited the researchers’ discovery of a “specific set of genes” changing.
As animals aged, shorter genes “appeared to become more active” than longer genes.
In humans, the top 5% of genes with the shortest transcripts “included many linked to shorter life spans such as those involved in maintaining the length of telomeres.”
Conversely, the researchers’ review of the leading 5% of genes in humans with the longest transcripts found an association with long lives.
Antiaging drugs—rapamycin (aka, sirolimus) and resveratrol—were linked to an increase in long-gene transcripts.
“The changes in the activity of genes are very, very small, and these small changes involve thousands of genes. We found this change was consistent across different tissues and in different animals. We found it almost everywhere,” Thomas Stoeger, PhD, postdoctoral scholar in the Amaral Lab who led the study, told GEN.
In their paper, the Northwestern scientists noted implications for creation of healthcare interventions.
“We believe that understanding the direction of causality between other age-dependent cellular and transcriptomic changes and length-associated transcriptome imbalance could open novel research directions for antiaging interventions,” they wrote.
While more research is needed to validate its findings, the Northwestern study is compelling as it addresses a new area of transcriptome knowledge. This is another example of researchers cracking open human and animal genomes and gaining new insights into the processes supporting life.
For clinical laboratories and pathologists, diagnostic testing to reverse aging and guide the effectiveness of therapies may one day be possible—kind of like science’s take on the mythical Fountain of Youth.
Clinical laboratories and pathology groups may soon have new assays for diagnosis, treatment identification, patient monitoring
It’s here at last! The human Y chromosome now has a full and complete sequence. This achievement by an international team of genetic researchers is expected to open the door to significant insights in how variants and mutations in the Y chromosome are involved in various diseases and health conditions. In turn, these insights could lead to new diagnostic assays for use by clinical laboratories and pathology groups.
Pathologists and clinical laboratories involved in genetic research will understand the significance of this accomplishment. The full Y chromosome sequence “fills in gaps across more than 50% of the Y chromosome’s length, [and] uncovers important genomic features with implications for fertility, such as factors in sperm production,” SciTechDaily noted.
This breakthrough will make it possible for other research teams to gain further understanding of the functions of the Y chromosome and how specific gene variants and mutations contribute to specific health conditions and diseases. In turn, knowledge of those genetic sequences and mutations would give clinical laboratories the assays that help diagnosis, identify relevant therapies, and monitor a patient’s progress.
“When you find variation that you haven’t seen before, the hope is always that those genomic variants will be important for understanding human health,” said Adam Phillippy, PhD, a senior investigator and head of the Genome Informatics Section at the National Human Genome Research Institute, in a press release. Clinical laboratories and anatomic pathology groups may soon have new assays based on the T2T study findings. (Photo copyright: National Human Genome Research Institute.)
Study Background and Recognition
Revolutionary thinking by the Telomere-to-Telomere (T2T) scientists led to the team’s breakthrough. The researchers “applied new DNA sequencing technologies and sequence assembly methods, as well as knowledge gained from generating the first gapless sequences for the other 23 human chromosomes,” SciTechDaily reported.
In 1977, the first complete genome of an organism was sequenced. Thus began the commencement of sequencing technology research. Twenty years ago the first human genome sequence was completed. The result was thanks to years of work through the preferred “chain termination” (aka, Sanger Sequencing) method developed by Fred Sanger and a $2.7 billion contribution from the Human Genome Project, according to a study published in the African Journal of Laboratory Medicine (AJLM).
By 2005, a new era in genomic sequencing emerged. Scientists now employed a technique called pyrosequencing and the change had great benefits. “Massively parallel or next-generation sequencing (NGS) technologies eliminated the need for multiple personnel working on a genome by automating DNA cleavage, amplification, and parallel short-read sequencing on a single instrument, thereby lowering costs and increasing throughput,” the AJLM paper noted.
The new technique brought great results. “Next-generation sequencing technologies have made sequencing much easier, faster and cheaper than Sanger sequencing,” the AJLM study authors noted.
The changes allowed more sequencing to be completed. Nevertheless, more than half of the Y chromosome sequence was still unknown until the new findings from the T2T study, SciTechDaily reported.
Why the TDT Breakthrough Is So Important
“The biggest surprise was how organized the repeats are,” said Adam Phillippy, PhD, a senior investigator and head of the NHGRI. “We didn’t know what exactly made up the missing sequence. It could have been very chaotic, but instead, nearly half of the chromosome is made of alternating blocks of two specific repeating sequences known as satellite DNA. It makes a beautiful, quilt-like pattern.”
Much can be gained in knowing more about the Y chromosome. Along with the X chromosome, it is significant in sexual development. Additionally, current research is showing that genes on the Y chromosome are linked to the risk and severity of cancer.
Might What Comes Next Give Clinical Labs New Diagnostic Tools?
The variety of new regions of the Y chromosome that the T2T team discovered bring into focus several areas of new genetic research. For instance, the “azoospermia factor region, a stretch of DNA containing several genes known to be involved in sperm production” was uncovered, and “with the newly completed sequence, the researchers studied the structure of a set of inverted repeats or palindromes in the azoospermia factor region,” SciTechDaily reported.
“This structure is very important because occasionally these palindromes can create loops of DNA. Sometimes, these loops accidentally get cut off and create deletions in the genome,” said Arang Rhie, PhD, a staff scientist at NHGRI and first author of the Nature study.
Missing regions would challenge the production of sperm, impacting fertility, so being able to finally see a complete sequence will help research in this area.
Scientists are only just beginning to recognize the value of this breakthrough to future genetic research and development. As genetic sequencing costs continue to drop, the T2T research findings could mean new treatment options for pathologists and diagnostic assays for clinical laboratories are just around the corner.
Though a ‘work in progress,’ the Oxford researchers who conducted the trail believe the MCED blood test could help doctors give better cancer assessments
Cancer is typically diagnosed through tissue biopsies that are often invasive and painful for patients. Now, recently-released results of a National Health Service (NHS) trial study of a relatively new multi-cancer early detection test (MCED) may provide a less painful/invasive cancer test experience to UK residents.
Developed by California-based healthcare technology company Grail, the clinical laboratory blood test—called Galleri—can detect 50 cancer types and, according to the company’s website, even identify the cancer’s location within the body. It is currently only available through a doctor’s prescription.
Researchers have long sought to improve screening methods and diagnostic technologies that identify cancers more easily and at an earlier stage. They recognize that a simple, inexpensive laboratory blood test—as opposed to a tissue biopsy—that detects both the presence of multiple cancer types and its location would benefit both medical professionals and patients worldwide.
“The [Galleri] test was 85% accurate in detecting the source of the cancer, and that can be really helpful because so many times it is not immediately obvious when you have got the patient in front of you what test is needed to see whether their symptoms are down to cancer,” said Mark Middleton, MD, PhD, head of the Department of Oncology at the University of Oxford and lead researcher of the study, in a BBC interview. (Photo copyright: University of Oxford.)
Details of the SYMPLIFY Study
To conduct the SYMPLIFY study, Oxford researchers enrolled 6,238 adults in England and Wales who were referred for imaging and diagnostic testing with symptoms that were indicative of gynecological, lung, or lower/upper GI cancers, or with non-specific symptoms. The most commonly reported symptoms that triggered the referrals were:
DNA from cancer cells—called ctDNA (circulating tumor DNA)—can be detected in blood samples at early tumor stages. The Galleri MCED test was performed on cell-free DNA taken from blood samples provided by the study participants. The test was performed in batches and blinded to results of previous diagnostic tests.
The predictions of the test were then compared to diagnoses received via traditional diagnostic testing and imaging.
According to the Oxford researchers’ Lancet paper, GRAIL’s MCED test detected a cancer signal in 323 of the study participants. Of those individuals, 244 received a cancer diagnosis, resulting in a positive predictive value (PPV) of 75.5%, a negative predictive value (NPV) of 97.6%, and a specificity of 98.4%.
The overall sensitivity of the Galleri test was 66.3%, representing a range from 24.2% in Stage 1 cancers to 95.3% in stage IV cancers. The mean age of the study participants was 62.1 years old, and the sensitivity increased with age and cancer stage.
The overall accuracy of the top Cancer Signal Origin (CSO) prediction following a positive MCED test was 85.2%, the researchers concluded.
“With that prediction from the test, we can decide whether to order a scope or a scan and make sure we are giving the right test the first time,” Mark Middleton, MD, PhD, head of the Department of Oncology at the University of Oxford and lead researcher of the study, told BBC News.
The most common cancers detected among the study participants were:
“Earlier cancer detection and subsequent intervention has the potential to greatly improve patient outcomes. Most patients diagnosed with cancer first see a primary care physician for the investigation of symptoms suggestive of cancer, like weight loss, anemia, or abdominal pain, which can be complex as there are multiple potential causes,” said Brian Nicholson, DPhil, Associate Professor at Oxford’s Nuffield Department of Primary Care Health Sciences and co-lead investigator for the study in a 2023 Oxford press release. “New tools that can both expedite cancer diagnosis and potentially avoid invasive and costly investigations are needed to more accurately triage patients who present with non-specific cancer symptoms.
“The high overall specificity, positive predictive value, and accuracy of the cancer signal detected and cancer signal origin prediction that was reported across cancer types in the SYMPLIFY study indicate that a positive MCED test could be used to confirm that symptomatic patients should be evaluated for cancer before pursuing other diagnoses,” he added.
MCED Test May Help Doctors Better Assess Cancer
The SYMPLIFY study is the first large-scale analysis of an MCED test in patients who were referred by their doctors for diagnostic testing due to suspected cancers. The results of the study were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in June.
Middleton told BBC News that the test is not yet accurate enough to “rule in or rule out cancer,” but it was useful for researchers and patients.
“The findings from the study suggest this test could be used to support GPs to make clinical assessments but much more research is needed, in a larger trial, to see if it could improve GP assessment and ultimately patient outcomes,” David Crosby, PhD, head of Prevention and Early Detection Research, Cancer Research, UK, told BBC News.
Clinical laboratories and anatomic pathology groups that perform tissue biopsy testing for oncologists will want to monitor the progress of this simple blood test that may someday reduce the number of invasive, painful biopsies required to diagnose cancer and other health considerations.
Findings may help clinical laboratories identify healthcare workers who could work on the front lines of the next pandemic without fear of serious infection
University of California San Francisco researchers have discovered a gene mutation that enables some people’s immune system to recognize and respond to a COVID-19 infection despite having no prior exposure to the SARS-CoV-2 coronavirus (which would produce antibodies against future infections).
This genetic advantage will be of interest to clinical laboratory professionals and pathologists involved in immune system testing. Why some individuals with COVID-19 show few if any symptoms has confounded microbiologists and virologists since the beginning of the pandemic. Now, the UC San Francisco (UCSF) scientists believe they know why.
Dark Daily previously covered the UCSF study in “UCSF Researchers Identify Genetic Mutation That Promotes an Asymptomatic Response in Humans to COVID-19 Infection.” We covered how variations in a specific gene in a system of genes responsible for regulating the human immune system appears to be the factor in why about 10% of those who become infected with the virus are asymptomatic. And we predicted that understanding why some people display no symptoms during a COVID-19 infection could lead to new precision medicine genetic tests medical laboratories could use to identify people with the mutated gene.
“If you have an army that’s able to recognize the enemy early, that’s a huge advantage,” said immunogeneticist Jill Hollenbach, PhD, in a UCSF news release. Hollenbach led the research team that identified a mutated gene responsible for immune response to COVID-19 in individuals who have not been exposed to the SARS-CoV-2 coronavirus. Clinical laboratory professionals and pathologists involved in immune system testing will find the UCSF study useful. (Photo copyright: Elena Zhukova /University of California San Francisco.)
UCSF Study Details
UCSF researchers discovered that individuals who are COVID-19 “super dodgers” have “a mutation in the proteins that helps the immune system recognize what belongs to the body and what doesn’t,” Euronews reported.
The UCSF study showed that HLA-B*15.01—a Human Leukocyte Antigen (HLA) mutation—informs the body of the presence of SARS-CoV-2, regardless of whether it has encountered the invader before. The immune system then deploys T-cells [white blood cells called lymphocytes that help the immune system fight germs and protect the body from disease] to “eliminate” the coronavirus.
“Individuals with this B*15:01 mutation who have these cross-reactive T-cells seem to be particularly effective, very early in infection, at nuking—for lack of a better word—the virus before these folks experience any symptoms at all,” Jill Hollenbach, PhD, and immunogeneticist and Professor in the Department of Neurology and Department of Epidemiology and Biostatistics at UCSF, told STAT. Hollenbach led the team that discovered the gene mutation responsible for COVID-19 super dodgers.
“The mutation—HLA-B*15:01—is quite common, carried by about 10% of the study’s population. It doesn’t prevent the virus from infecting cells but, rather, prevents people from developing any symptoms. That includes a runny nose or even a barely noticeable sore throat,” according to a UCSF news release, which added, “UCSF researchers found that 20% of people in the study who remained asymptomatic after infection carried at least one copy of the HLA-B*15:01 variant, compared to 9% of those who reported symptoms. Those who carried two copies of the variant were far more likely—more than eight times—to avoid feeling sick.”
To find study participants, the team consulted The National Marrow Donor Program (NMDP) Be the Match Registry, which pairs donors with people needing transplants. It’s the largest registry of HLA volunteer donors in the United States. “Researchers suspected early on that HLA was involved, and fortunately a national registry existed that contained the data they were looking for,” the UCSF news release states.
To fully understand how COVID-19 affected the NMDP donors, the team utilized UCSF’s COVID-19 Citizen Science Study, a longitudinal cohort study on UCSF’s Eureka Digital Research Platform which uses a smartphone app developed by UCSF to learn how to predict SARS-CoV-2’s spread throughout the world and combat it.
About 30,000 people from the registry were followed through that first year of the COVID-19 pandemic, which featured frequent testing and no vaccine access for most, UCSF stated.
“We did not set out to study genetics, but we were thrilled to see this result come from our multidisciplinary collaboration with Dr. Hollenbach and the National Marrow Donor Program,” said internal medicine physician Mark Pletcher, MD, Professor of Epidemiology and Biostatistics at UCSF, in the news release. Pletcher’s practice focuses on prevention of cardiovascular disease.
The UCSF scientists dove deep to understand how HLA-B*15:01 tackled coronavirus, and together with researchers from La Trobe University in Australia, “They homed in on the concept of T-cell memory, which is how the immune system remembers previous infections,” UCSF reported.
“It’s just one of these natural lucky breaks,” Hollenbach told STAT.
UCSF Findings Bring Hope for Improved Vaccines and Drug Therapies
HLA was a good hunch to follow. The UCSF researchers’ Nature paper claimed HLA to be “the most polymorphic and medically important human genomic region.” It noted that variations of HLA were linked to myriad diseases, especially viral infections.
“The strongest associations were seen with viral infections, and HLA was associated with rapid progression and viral load of human immunodeficiency virus (HIV), hepatitis B, and C … Also HLA class I and II alleles have been associated with severe acute respiratory syndrome caused by SARS-CoV,” the Nature paper noted.
“Specific focus on asymptomatic infection has the potential to further our understanding of disease pathogenesis and supports ongoing efforts towards vaccine development and the identification of potential therapeutic targets,” the UCSF researchers wrote in Nature.
Should further research and studies confirm these findings, it’s reasonable to speculate that, in a future outbreak of new strains of SARS-CoV-2, clinical laboratories could test individuals to identify those with the mutation making them unlikely to experience a serious infection.
Those individuals could work on the front lines of medical care with a lower risk of infection and serious disease. It might also mean that they would not need vaccinations at all.
Technology enables sampling of an individual’s microbiome over time to observe changes associated with different illnesses or different diets
There is now a pill-sized device that can non-invasively collect and deliver a sample of gut bacteria taken directly from specific areas of a person’s gastrointestinal (GI) tract. One benefit of this new technology is that it can collect samples from the upper digestive system. Although not ready for clinical use, this is the kind of technology that would enable microbiologists and clinical laboratory scientists to add more microbiome assays to their test menu.
Researchers at Stanford University, Envivo Bio, and the University of California, Davis (UC Davis) have developed a vitamin capsule-sized device—dubbed CapScan—that can measure the microbial, viral, and bile acid profiles contained in the human intestines as it passes through on its way to being expelled.
Currently, scientists rely on stool samples to collect similar data as they are easy to gather and readily available. However, stool samples may not provide the most accurate analysis of the various microorganisms that reside in the human gut.
“Measuring gut metabolites in stool is like studying an elephant by examining its tail,” said Dari Shalon, PhD, Founder and CEO at Envivo Bio, one of the authors of the study, in a UC Davis news release. “Most metabolites are made, transformed, and utilized higher up in the intestines and don’t even make it into the stool. CapScan gives us a fuller picture of the gut metabolome and its interactions with the gut microbiome for the first time.” Shalon is the inventor of the CapScan device.
This demonstrates how technological advancements are giving scientists new diagnostic tools to guide selection of therapies and to monitor a patient’s progress.
Microbiologists will take a special interest in this published study because, once confirmed by further studies, it would provide microbiology laboratories and clinical labs with a new way to collect samples. In clinical laboratories throughout the country, handling fecal specimens is considered an unpleasant task. Once cleared for clinical use, devices like CapScan would be welcomed because the actual specimen would be contained within the capsule, making it a cleaner, less smelly specimen to handle than conventional fecal samples.
“This capsule and reports are the first of their kind,” said Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis, in a news release. “All other studies on human gut microbiota focused on stool as a surrogate for colon metabolism. However, of course, the fact is that 90% of human digestion happens in the upper intestine, not the colon.” Clinical laboratories have long worked with stool samples to perform certain tests. If CapScan proves clinically viable, labs may soon have a new diagnostic tool. (Photo copyright: UC Davis.)
Collecting Small Intestine Microbiota
Human digestion occurs mostly in the small intestine where enzymes break down food particles so they can later be absorbed through the gut wall and processed in the body. Stool samples, however, only sample the lower colon and not the small intestine. This leaves out vital information about a patient.
“The small intestine has so far only been accessible in sedated people who have fasted, and that’s not very helpful,” Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis and one of the study authors, said in the news release.
According to their Nature paper, to perform their research the team recruited 15 healthy adults to participate in the study. Each participant swallowed four CapScan “pills,” either twice daily or on two consecutive days. The pills were designed to respond to different pH (potential of hydrogen) levels.
Each pill’s pH-sensitive outer coating enables scientists to select which area of the intestinal tract to sample. The outer coating dissolves at a certain point as it travels from the upper intestine to the colon. When this happens, a one-way valve gathers miniscule amounts of biofluids into a tiny, inflatable bladder. Once full, the bladder seals shut and the CapScan continues its journey until it is recovered in the stool. The researchers then genetically sequenced the RNA from the collected samples.
The scientists discovered that the microbiome varied substantially at distinctive sections of the GI tract. When compared to collected stool samples, the researchers determined that traditional stool sampling could not capture that variability.
“There’s enormous potential as you think about how the environment is changing as you go down the intestinal tract,” Kerwyn Huang, PhD, Professor of Bioengineering and of Microbiology and Immunology at Stanford, one of the authors of the study, told Drug Discovery News. “Identifying how something like diet or disease affects the variation in the individual microbiome may even provide the potential to start discovering these important health associations.”
The genetic sequencing also revealed which participants had taken antibiotics within one to five months before the study because their data was so incongruous with the other participants. Those individuals had distinctive differences in their microbiome and bile acid composition, which illustrates that antibiotics can potentially affect gut bacteria even months after being taken.
Researchers Use Multiple ‘Omics’ Approach
The researchers used “multiomics” to analyze the samples. They identified the presence of 2,000 metabolites and found associations between metabolites and diet.
According to the Envivo Bio website, the CapScan allows for the regional measurement of:
“Overall, this device can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease,” Fiehn said in the press release.
Future of Collecting Gut Bacteria
Using CapScan is a non-invasive procedure that makes it possible to sample an individual’s microbiome once, or to monitor it over time to observe changes associated with different illnesses or diets. Since it takes time for the device to pass through the digestive system, it is not a rapid test, but initial studies show it could be more accurate than traditional clinical laboratory testing.
“This technology makes it natural to think about sampling from many places and many times from one person, and it makes that straightforward and inexpensive,” Huang said.
Advancements in technology continue to provide microbiology and clinical laboratories with new, innovative tools for diagnosing and monitoring diseases, as well as guiding therapy selection by medical professionals. Though more research and clinical studies are needed before a device like the CapScan can be commonly used by medical professionals, it may someday provide a cutting-edge method for collecting microbiome samples.
Advances in genome sequencing give virologists and microbiologists new tools for tracking SARS-CoV-2 variants to their sources
Wastewater surveillance has emerged as an essential tool in the detection and tracking of the SARS-CoV-2 coronavirus within communities. Though COVID-19 infections are decreasing in the United States—and clinical laboratories are performing fewer diagnostic tests for the disease—researchers continue to monitor populations for the presence of the coronavirus and its variants to be prepared for the next outbreak.
Genetic sequencing of samples extracted from sewer systems throughout the country have revealed dozens of strains of the coronavirus containing multiple mutations in unusual combinations called cryptic genetic variants (CVG), also known as cryptic lineages. A recent study has indicated that wastewater may also provide answers to questions about long COVID as these mutations can be traced back to individuals who are living with chronic COVID-19 infections.
“Because increases in wastewater [viruses] generally occur before corresponding increases in clinical cases, wastewater surveillance serves as an early warning system for the emergence of COVID-19 in a community,” said Amy Kirby, PhD (above), CDC program lead for the National Wastewater Surveillance System, during a media telebriefing. Wastewater testing for viruses and bacteria may eventually lead to the implementation of systems to alert clinical laboratories in a region whenever infectious agents are detected in wastewater. (Photo copyright: Center for Global Safe Water, Sanitation, and Hygiene.)
Humans Found to Be Primary Source of Cryptic Lineages
To conduct their study, scientist at the University of Wisconsin-Madison and the University of Missouri School of Medicine examined the evolution of a SARS-CoV-2 Omicron subvariant found in wastewater coming from a single facility in Wisconsin that employed about 30 people. The researchers discovered the mutation had been present in the wastewater for more than a year.
Dark Daily originally covered their findings in “New, Cryptic COVID-19 Lineage Found in Ohio Wastewater by Molecular Virologist Tracking Spread of SARS-CoV-2 Variants.” We reported how scientists had tracked the lineage of the cryptic strain to Ohio, where it appeared to have originated from one individual who travels regularly between the cities of Columbus and Washington Court House. They believed the person had a form of long COVID and was unaware that he or she was infected with the coronavirus.
According to Marc Johnson, PhD, Professor of Microbiology and Immunology at the University of Missouri and one of the authors of the study, the individual who shed the mutations had been shedding at least a thousand times more COVID-19 virus than an average infected person sheds. The scientists examined other wastewater monitoring data and identified 37 related cases in the US. They concluded that humans are the main source of the cryptic lineages.
“The fact that someone can have this kind of infection—and there’s every indication that they are still an active member of society and not just lying in the hospital—it’s just amazing,” Johnson told CNN.
Wastewater Surveillance Not an Exact Science, CDC Says
Although not directly involved in this study, through its National Wastewater Surveillance System (NWSS) the US Centers for Disease Control and Prevention (CDC) has been tracking wastewater surveillance programs. The federal agency believes cryptic lineages do not pose a threat to public health.
“The signal we really look for is specific variants increasing in frequency in a community, because that’s what happens at the beginning of a variant surge,” Amy Kirby, PhD, Health Scientist, National Wastewater Surveillance System Lead for the CDC, told CNN. “And it’s not what we’re seeing with these cryptic lineages.”
Kirby also noted that wastewater surveillance is not an exact science and that many factors can impede the interpretation of the data. The mutations observed for this study could be from people with long COVID or even from an infected animal. To be certain of the results, she said, researchers would have to directly link the genetic sequence from a clinical test to a specific wastewater sample.
“Best-case scenario is you find the person, they have long COVID but had no idea they had this infection, and you get them with a doctor who can get them on medicines that will actually give their immune system a bit of an upper hand, and they get better,” Johnson told CNN. “But we only know about the ones we can find, and we don’t know what the implications are, because we still don’t know who those people are.”
Public health messaging in local communities is needed to raise awareness. But though tracking down specific infected individuals could help them receive medical attention, it may not be the most desirable course of action.
“Part of the power of wastewater surveillance is that it is inherently anonymous. It’s a community-level surveillance method,” Kirby said. “And so, tracking back through the wastewater system to identify a person is not what the system is intended for.”
Clinical Laboratories Play Key Role in Public Health
The cryptic lineage that Johnson and his team identified was a mutation that appeared in two watersheds in Ohio—one located in southern Columbus and one in the town of Washington Court House, which is about 40 miles south of Columbus. The researchers hypothesized that an individual living in that area had COVID for more than two years and did not know it, was most likely asymptomatic, and lives in one area and spends a lot of time (perhaps working) in the other area.
“There is almost zero chance the patient in Ohio knew about their infection. There is almost zero chance their doctor would figure it out. It is very likely the infection is causing long term damage,” Johnson wrote in a Twitter tweet. “I’m glad that there is a chance now that they might get appropriate care.”
Wastewater surveillance has materialized as a common method of identifying and monitoring strains of COVID-19 and other infectious diseases. And clinical laboratories play a key role in that process. With genetic sequencing technologies becoming more advanced, lower in cost, faster and more accurate, it’s feasible that those technologies will be utilized more to direct public health initiatives.
