All-of-Us program is free to participants and provides data to more than 800 research studies for cancer, COVID-19, Alzheimer’s, and other diseases; findings will lead to new biomarkers for clinical laboratory tests
It is hard to say no to free. At least that is what the National Institutes of Health (NIH) is counting on to help increase the size and diversity of its database of genetic sequences. The NIH’s All-of-Us Research Program is offering free genetic testing for all participants in the program, as well as free wearable Fitbits for those selected to provide lifestyle and behavior data.
Many pathologists and clinical laboratory managers know that this group of researchers hope to build a database of more than one million genetic sequences to better understand “how certain genetic traits affect underrepresented communities, which could greatly affect the future of customized healthcare,” CBS affiliate 8 News Now reported.
“Customized healthcare” is a euphemism for precision medicine, and genetic sequencing is increasingly playing a key role in the development of personalized diagnostics and therapeutics for cancer and other deadly diseases.
In “VA’s ‘Million Veterans Program’ Research Study Receives Its 100,000th Human Genome Sequence,” Dark Daily described how the NIH’s All-of-Us program was launched in 2018 to aid research into health outcomes influenced by genetics, environments, and lifestyle. At that time, the program had biological samples from more than 270,000 people with a goal of one million participants.
Matthew Thombs, Senior Project Manager of Digital Health Technology at Scripps Research in La Jolla, Calif., joined the All-of-Us program after losing a family member “to a condition I believe could have been managed with changes to their lifestyle,” he told 8 News Now.
“What we are building will empower researchers with the information needed to make such conclusions (about possible need to change lifestyles) and forever alter how diseases are treated,” he added. “I hope that what we are doing here will help my son grow up in a world where healthcare is more of a priority, and many of the ailments we see today are things of the past.”
Such genetic testing could discover biomarkers for future personalized clinical laboratory diagnostics and drug therapies, a key aspect of precision medicine.
The photo above shows an All-of-Us participant being prepped to provide a biological sample for genetic testing. According to Matthew Thombs, Senior Project Manager of Digital Health Technology at Scripps Research, “participants can provide as much or as little information as they like, every single data point matters.” The collected data is shared anonymously with more than 800 research studies for COVID-19, Alzheimer’s, cancer, and other diseases, 8 News Now reported. (Photo copyright: KLAS-TV.)
Scripps Research Integrates Mobile Health Technology into All-of-Us Program
A critical aspect of the NIH’s research is determining how people’s behavior combined with their genetics may predispose them to certain diseases. Nonprofit research institution Scripps Research is working with the NIH’s All of Us Research Program to enroll and collect biological samples from one million US residents.
In addition, Scripps is fitting study participants with wearable mobile health devices to capture data on their habits and lifestyles.
“Until now, the treatment and prevention of disease has been based on a ‘one-size-fits-all’ approach, with most therapeutics tailored for the ‘average patient’. However, advances in genomic sequencing, mobile health technologies, and increasingly sophisticated informatics are ushering in a new era of precision medicine. This new approach takes into account differences in people’s genes, environment, and lifestyles giving medical professionals resources to design targeted treatments and prevention strategies for the individual,” Scripps states on its website.
Can wearable fitness devices and related data contribute to research on genetics and healthcare outcomes? Scripps aims to find out. It has fitted 10,000 people in the All-of-Us program with Fitbit devices (Fitbit Charge 4 tracker or Fitbit Versa 3 smartwatch) at no cost. Since February, Scripps has distributed 10,000 Fitbit wearable devices through the All-of-Us program.
“By sharing information about their health, habits, and environment, participants will help researchers understand why people get sick or stay healthy,” the Scripps website adds.
The Scripps researchers plan to analyze how the people use the wearable devices. They are also accumulating data about participants’ physical activity, heart rate, sleep, and other health metrics and outcomes “as part of the broader All of Us program,” a Scripps news release explained.
“This is the first time All of Us is distributing devices to participants. Our goal is to better understand how participants engage during research studies in order to continually improve user experience and participation. We also expect to learn more about how wearable data may inform the personalization of healthcare,” said Julia Moore Vogel, PhD, Director of The Participant Center at the All of Us Research Program at Scripps Research, in the news release.
All-of-Us Program Records ‘Significant Progress in Participant Diversity’
As of June, the NIH has enrolled 386,000 participants into the All-of-Us program, with 278,000 consenting to all of the program’s steps. Eighty percent of biological samples in the collection are from people in communities that have been under-represented in previous biomedical research an NIH new release noted. According to the NIH, that gives the All-of-Us research program “the most diverse dataset.”
What will all this research ultimately bring to clinical laboratories? Who knows? Nevertheless, if federal institutions like the NIH and non-profit research companies like Scripps believe precision medicine is worth investing in, then the All-of-Us program is worth watching.
A diverse database of a million genetic sequences combined with lifestyle and behavioral data may lead to new and improved personalized diagnostics and drug therapies.
As many clinical laboratory scientists know, gene sequencing technology continues to become faster, more accurate, and less expensive per whole human genome sequenced
In February, Dark Daily reported that Personalis, Inc. (NASDAQ:PSNL) had delivered its 100,000th whole human genome sequence to the US Department of Veterans Affairs Million Veterans Program (VA MVP). Now, the Menlo Park, Calif.-based cancer genomics company has topped that achievement by delivering its 125,000 whole human genome sequence!
“This represents another important landmark for both the program and for Personalis,” said John West, Chief Executive Officer, Personalis, in a news release. “We congratulate the VA MVP for reaching this important milestone.
“We strongly believe that the research projects being performed today will enable precision medicine in healthcare systems in the future across a wide range of disease areas,” he added. This is a positive development for clinical laboratories, as personalized medicine services require a lab to sequence and interpret the patient’s DNA.
Personalis was contracted with the US federal government to perform genetic research in 2012 and has delivered 50,000 genomes to the VA MVP during the past twelve months.
The Personalis and VA MVP researchers seek to gain a better understanding of how genetic variants affect health. Before the COVID-19 pandemic hit the US, the VA was enrolling veterans in the Million Veterans Program at 63 VA medical centers across the country. There are currently about 830,000 veterans enrolled in the venture and the VA is expecting two million veterans to eventually sign up for the sequencing project.
“As a global leader in genomic sequencing and comprehensive analytics services, Personalis is uniquely suited to lead these population-scale efforts and we are currently in the process of expanding our business operations internationally,” West added.
According to the press release, “the VA MVP provides researchers with a rich resource of genetic, health, lifestyle, and military-exposure data collected from questionnaires, medical records, and genetic analyses. By combining this information into a single database, the VA MVP promises to advance knowledge about the complex links between genes and health.”
NIH All of Us Research Program Supports Precision Medicine Goals Another genetic research project being conducted by the US National Institutes of Health (NIH) is the All of Us Research Program. Using donated personal health information from thousands of participants, the NIH researchers seek to “learn how our biology, lifestyle, and environment affect health,” according to the program’s website.
“We’re changing the paradigm for research,” said Josh Denny, MD (above), Chief Executive Officer of the All of Us Research Program, in an NIH news release. “Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science they’re making possible. We’re working to provide that valuable information in a responsible way,” he added. Clinical laboratories may soon see new precision medicine biomarkers derived from this type of research. (Photo copyright: Vanderbilt University.)
The All of Us Research Program intends to have at least one million US participants take part in the research. The researchers hope to help scientists discover new knowledge regarding how biological, environmental, and behavioral factors influence health, and to learn to tailor healthcare to patients’ specific medical needs, a key component of precision medicine.
Participants in the project share personal information via a variety of methods, including surveys, electronic health records, and biological samples.
A Better Sampling of Under-Represented Communities
Since opening enrollment in 2018, more than 270,000 people have contributed blood, urine, and saliva samples to the All of Us Research Program. More than 80% of the participants come from communities that are traditionally under-represented in biomedical research.
“We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone,” said Brad Ozenberger, PhD, Genomics Program Director, All of Us, in the NIH news release. “Too many groups have been left out of research in the past, so much of what we know about genomics is based mainly on people of European ancestry. And often, genomic data are explored without critical context like environment, economics, and other social determinants of health. We’re trying to help change that, enabling the entire research community to help fill in these knowledge gaps.”
The All of Us Research Project’s analysis of the collected data includes both whole-genome sequencing (WGS) and genotyping and is taking a phased approach in returning genetic data to participants.
Participants initially receive data about their genetic ancestry and traits. That is followed later by health-related results, such as how their genetic variants may increase the risk of certain diseases and how their DNA may affect their reaction to drug therapies.
Genetic researchers hope programs like these will lead to improved in vitro diagnostics and drug therapies. Genetic sequencing also may lead to new diagnostic and therapeutic biomarkers for clinical laboratories.
New USPSTF guidelines suggest reducing the volume of Vitamin D deficiency testing in the general population, which could reduce revenue for clinical laboratories
From 2005 to 2011, the volume of clinical laboratory tests for Vitamin D soared nationally as more doctors tested more patients for Vitamin D deficiency. This became a major source of revenue growth for many clinical laboratories performing those tests. But at least a portion of lab revenue associated with Vitamin D testing may be in jeopardy.
In a recommendation statement published in JAMA Network, titled, “Screening for Vitamin D Deficiency in Adults,” the United States Preventive Services Task Force (USPSTF)—following up on its 2014 recommendations—stated “that the current evidence is insufficient to assess the balance of benefits and harms of screening for Vitamin D deficiency in asymptomatic adults.”
The USPSTF’s new recommendations concerning Vitamin D testing came after the federal task force performed an extensive review of the benefits and potential harm of screening for Vitamin D deficiencies in non-pregnant adults who displayed no symptoms of a deficiency. Symptoms of a Vitamin D deficiency include fatigue and tiredness, bone and back pain, depression, impaired would healing, bone loss, hair loss, and muscle pain.
After completing its research, the USPSTF concluded “the overall evidence on the benefits of screening for Vitamin D deficiency is lacking. Therefore, the balance of benefits and harms of screening for Vitamin D deficiency in asymptomatic adults cannot be determined.”
Are USPSTF Conclusions Contrary to Current Deficiency Testing Practices?
“Among asymptomatic, community-dwelling populations with low Vitamin D levels, the evidence suggests that treatment with Vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the JAMA Network article states.
Other studies have linked low Vitamin D levels with some health conditions and risks, however, the USPSTF review found no studies that directly evaluated any perks associated with Vitamin D screening in otherwise healthy individuals.
Everyday Health listed 10 illnesses linked to low Vitamin D deficiency. They include:
“We see a lot of associations between Vitamin D deficiency and poor health outcomes,” Mary Byrn, PhD, RN, an associate professor at Loyola University in Chicago who studies Vitamin D, told Everyday Health. “Although these are relationships and we are unable to conclude cause and effect, taking Vitamin D supplements or exposing yourself to the sun in a safe manner to increase Vitamin D naturally are easy ways to improve your health and try to reduce your risk of multiple diseases,” she said. (Photo copyright: Midwest Nursing Research Society.)
Can Vitamin D Supplementation Be Harmful?
The USPSTF study also stated that Vitamin D supplementation appears to be safe and that toxicity from too much Vitamin D would be rare. One of the USPSTF’s key concerns of screening for Vitamin D in asymptomatic individuals was the potential for misclassification and inaccurate diagnoses.
The study also revealed that more research is needed to determine what serum levels are optimal when diagnosing a Vitamin D deficiency, and whether those levels vary by subgroups, such as race, ethnicity, or gender.
The JAMA Network article states that “the evidence is inconclusive about the effect of treatment on physical functioning and infection.”
The amount of Vitamin D individuals need each day depends upon their age. The National Institutes of Health (NIH) recommends that adults between the ages of 19 and 70 get 15 micrograms or 600 International Units (IU) of Vitamin D daily.
According to an NIH fact sheet, people can receive Vitamin D through sun exposure, supplements, and some food, such as fatty fish, mushrooms, beef liver, cheese, and egg yolks, plus foods that are fortified with Vitamin D, such as some milk products and breakfast cereals.
Vitamin D and COVID-19
It has been widely reported that approximately 42% of Americans are Vitamin D deficient. And Vitamin D deficiency has been linked to an increased risk of contracting the SARS-CoV-2 coronavirus and how well patients recover after COVID-19 treatment.
A study published in the Journal of Clinical Endocrinology and Metabolism that examined 216 COVID-19 hospitalized patients in Spain found that over 80% of those individuals were deficient in Vitamin D. The study also found that COVID-19 patients who had lower Vitamin D levels also had a higher number of inflammatory markers that have been associated with poorer COVID-19 outcomes. The results of this study were in March.
For several decades, experts have recommended avoiding sun exposure and using sunscreen to avoid skin cancers. This may have caused people to get less Vitamin D from sun exposure. It may also have contributed to an increase in the number of Vitamin D deficiencies and increased COVID-19 infections.
Pathologists and clinical laboratory managers should keep in mind that the USPSTF recommended less testing for Vitamin D deficiencies in asymptomatic individuals. This proposal may affect test volume in clinical laboratories, as Vitamin D testing has been a common and lucrative assay for many years.
With improved genetic sequencing comes larger human genome databases that could lead to new diagnostic and therapeutic biomarkers for clinical laboratories
As the COVID-19 pandemic grabbed headlines, the human genome database at the US Department of Veterans Affairs Million Veterans Program (MVP) quietly grew. Now, this wealth of genomic information—as well as data from other large-scale genomic and genetic collections—is expected to produce new biomarkers for clinical laboratory diagnostics and testing.
In December, cancer genomics company Personalis, Inc. (NASDAQ:PSNL) of Menlo Park, Calif., achieved a milestone and delivered its 100,000th whole human genome sequence to the MVP, according to a news release, which also states that Personalis is the sole sequencing provider to the MVP.
The VA’s MVP program, which started in 2011, has 850,000 enrolled veterans and is expected to eventually involve two million people. The VA’s aim is to explore the role genes, lifestyle, and military experience play in health and human illness, notes the VA’s MVP website.
Health conditions affecting veterans the MVP is researching include:
The VA has contracted with Personalis through September 2021, and has invested $175 million, Clinical OMICS reported. Personalis has earned approximately $14 million from the VA. That’s about 76% of the company’s revenue, according to 2nd quarter data, Clinical OMICS noted.
“The VA MVP is the largest whole genome sequencing project in the United States, and this is a significant milestone for both the program and for Personalis,” said John West (above with wife Judy), Founder and CEO of Personalis, in the news release. “Population-scale sequencing projects of this nature represent a cornerstone in our effort to accelerate the advancement of precision medicine across a wide range of disease areas,” he added. (Photo copyright: MIT Technology Review.)
Database of Veterans’ Genomes Used in Current Research
What has the VA gained from their investment so far? An MVP fact sheet states researchers are tapping MVP data for these and other veteran health-related studies:
Differentiating between prostate cancer tumors that require treatment and others that are slow-growing and not life-threatening.
How genetics drives obesity, diabetes, and heart disease.
How data in DNA translates into actual physiological changes within the body.
Gene variations and patients’ response to Warfarin.
NIH Research Program Studies Effects of Genetics on Health
Another research program, the National Institutes of Health’s All of Us study, recently began returning results to its participants who provided blood, urine, and/or saliva samples. The NIH aims to aid research into health outcomes influenced by genetics, environment, and lifestyle, explained a news release. The program, launched in 2018, has biological samples from more than 270,000 people with a goal of one million participants.
“We’re changing the paradigm for research. Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science they’re making possible,” said Josh Denny, MD, CEO of the NIH’s All of Us research program in the news release. Denny, a physician scientist, was Professor of Biomedical Informatics and Medicine, Director of the Center for Precision Medicine and Vice President for Personalized Medicine at Vanderbilt University Medical Center prior to joining the NIH. (Photo copyright: National Institutes of Health.)
Inclusive Data Could Aid Precision Medicine
The news release notes that more than 80% of biological samples in the All of Us database come from people in communities that have been under-represented in biomedical research.
“We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone,” said Brad Ozenberger, PhD, All of Us Genomics Program Director, in the news release.
Precision medicine designed for specific healthcare populations is a goal of the All of Us program.
“[All of Us is] beneficial to all Americans, but actually beneficial to the African American race because a lot of research and a lot of medicines that we are taking advantage of today, [African Americans] were not part of the research,” Chris Crawford, All of US Research Study Navigator, told the Birmingham Times. “As [the All of Us study] goes forward and we get a big diverse group of people, it will help as far as making medicine and treatment that will be more precise for us,” he added.
Large Databases Could Advance Care
Genome sequencing technology continues to improve. It is faster, less complicated, and cheaper to sequence a whole human genome than ever before. And the resulting sequence is more accurate.
Thus, as human genome sequencing databases grow, researchers are deriving useful scientific insights from the data. This is relevant for clinical laboratories because the new insights from studying bigger databases of genomic information will produce new diagnostic and therapeutic biomarkers that can be the basis for new clinical laboratory tests as well as useful diagnostic assays for anatomic pathologists.
Clinical laboratory professionals should note that one case study describes a COVID-positive cancer patient shedding infectious particles for five months, which is much longer than expected
Just when researchers start believing they understand COVID-19 infections, something happens that reveals there is still more to learn. These additional findings are relevant for clinical laboratory managers and pathologists because the new insights often may play a role in how SARS-CoV-2 results should be interpreted for individual patients.
Researchers recently described a case where, in February, a 71-year-old woman underwent surgery related to her 10-year battle with cancer. While she was in the hospital, she was found to be positive for the SARS-CoV-2 coronavirus, though she showed no respiratory or systemic symptoms. Nevertheless, the hospital isolated her and monitored the infection.
To everyone’s surprise, the patient remained positive for five months. She underwent 15 COVID-19 tests from various diagnostics companies, as well as receiving two doses of convalescent plasma therapy, but she remained positive for the coronavirus into June.
In their published study, they wrote, “Although it is difficult to extrapolate from a single individual, our data suggest that long-term shedding of infectious virus may be a concern in certain immunocompromised people. Given that immunocompromised individuals could have prolonged shedding and may not have typical symptoms of COVID-19, symptom-based strategies for testing and discontinuing transmission-based precautions, as recommended by the Centers for Disease Control and Prevention (CDC), may fail to detect whether certain individuals are shedding infectious virus.”
Clinical laboratory professionals and pathologists will find it significant that patients with major health conditions may be shedding viral material for weeks longer than originally thought. This is relevant because it may be prudent to COVID test patients who present with compromised immune systems, and who are asymptomatic, and then repeat that testing at appropriate intervals.
The graphic above taken from the NIAID study shows how long it took for the SARS-CoV-2 coronavirus to clear the 71-year-old immunocompromised cancer patient’s system, and at which points the convalescent plasma doses were administered. (Graphic copyright: National Institute of Allergy and Infectious Diseases.)
Immunocompromised Patients May Handle COVID-19 Differently
The NIAID researchers believe the reason the patient continued to shed infectious virus for so long was because she was immunocompromised. They wrote, “Many current infection control guidelines assume that persistently PCR-positive individuals are shedding residual RNA and not infectious virus, with immunocompromised people thought to remain infectious for no longer than 20 days after symptom onset. Here we show that certain individuals may shed infectious, replication-competent virus for much longer than previously recognized. Although infectious virus could be detected up to day 70, sgRNA, a molecular marker for active SARS-CoV-2 replication, could be detected up until day 105.”
In the United States, some three million people have compromised or weakened immune systems. This is a significant population, Science Alert reported.
“As the virus continues to spread, more people with a range of immunosuppressing disorders will become infected, and it’s more important to understand how SARS-CoV-2 behaves in those populations,” Vincent Munster, PhD, Chief, Virus Ecology Unit at the National Institute of Allergy and Infectious Diseases and co-author of the NIAID study, told Science Alert.
The NIAID study findings match knowledge about other coronaviruses. For example, Science Alert reported that immunocompromised people with Middle East Respiratory Syndrome (MERS) have been shown to shed common seasonal coronaviruses for up to a month following infection.
That study included 303 patients, of which 193 were symptomatic. During the course of the study, 21 of the asymptomatic patients developed symptoms, however, the viral load was similar in all of the patients, regardless of symptoms.
“Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2,” concluded the JAMA researchers. But how long should asymptomatic patients remain isolated?
Official Guidance Is Based on Symptoms
The CDC updated its guidelines for who should isolate and for how long in October. The guidelines cover:
People who have or had COVID-19 and had symptoms;
People who tested positive for COVID-19 but did not have symptoms;
People who either had severe symptoms of COVID-19 or who have a compromised immune system;
People who were exposed to COVID-19, and
People who have been reinfected.
Regarding those who are immunocompromised and had COVID-19, the CDC says they “may require testing to determine when they can be around others.”
In addition to noting that people who are immunocompromised may require additional testing, the CDC is also continuously updating its published list of people who are at risk for complications and severe illness if they contract COVID-19. However, as the NIAID study showed, even those with underlying medical conditions can be asymptomatic.
And as the NIAID researchers note, there is more to learn. “Understanding the mechanism of virus persistence and eventual clearance will be essential for providing appropriate treatment and preventing transmission of SARS-CoV-2 because persistent infection and prolonged shedding of infectious SARS-CoV-2 might occur more frequently. Because immunocompromised individuals are often cohorted in hospital settings, a more nuanced approach to testing these individuals is warranted, and the presence of persistently positive people by performing SARS-CoV-2 gRNA and sgRNA analyses on clinical samples should be investigated.”
SARS-CoV-2 Science Is Young
An additional takeaway for pathology lab professionals is the reminder that the scientific research surrounding the novel coronavirus that causes COVID-19 is very young. New insights and understanding will continue to emerge, probably for many years.
One reason why the development of vaccines for COVID-19 has been so quick is that it built on scientific knowledge of the first SARS outbreak and MERS. It’s interesting to note that both SARS and MERS are relatively new as well: SARS emerged in 2002 and MERS in 2012. Compared to a disease like HIV, which was first identified in 1959, scientists have only been working on these particular coronaviruses for a short period of time.
The NIAID study is yet another example of new knowledge and insights emerging about how SARS-CoV-2 infects individuals. Collectively, these findings make it challenging for medical laboratory professionals to stay current with everything relevant and associated with the proper interpretation of COVID-19 test results.
