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.
Clinical laboratory managers may want to follow the debate that surfaced shortly after publication of the study in a peer-reviewed journal, when editors of the journal issued concerns over the researchers’ claims
Virologists and medical laboratory scientists continue to investigate ways the SARS-CoV-2 coronavirus can be defeated using the body’s own defenses in conjunction with medical treatments and a possible vaccine. Now, researchers at the Boston University School of Medicine have discovered that higher levels of vitamin D in the blood may improve chances of recovering from a COVID-19 infection.
“This study provides direct evidence that Vitamin D sufficiency can reduce the complications, including the cytokine storm (release of too many proteins into the blood too quickly) and ultimately death from COVID-19,” Michael F. Holick, PhD, MD, Professor of Medicine, Physiology and Biophysics at Boston University School of Medicine and one of the authors of the study, told SciTechDaily.
Holick is well-known in the scientific community for his many published studies on Vitamin D. In 2018, Kaiser Health News and The New York Times published a retrospective on Holick and his advocacy on behalf of Vitamin D, titled, “The Man Who Sold America On Vitamin D—and Profited in the Process.” In that story, Holick acknowledged working as a consultant for several organizations, including Quest Diagnostics in a relationship that dates back to 1979. KHN and NYT noted that Quest Diagnostics performs Vitamin D tests.
The Boston University researchers published their study in PLOS ONE, a peer-reviewed open-access scientific journal published by the Public Library of Science (PLOS). The paper’s apparent conclusions, however, invoked an “expression of concern” from the journal’s editors, which, along with direct responses from the Boston University researchers, can be read on PLOS ONE.
Can Vitamin D Save Lives?
To perform their research, the Boston University researchers examined the Vitamin D levels of 235 patients who had been admitted to a hospital with a SARS-CoV-2 infection. The patients were then tracked for clinical outcomes, including:
Blood samples were also analyzed for the number of lymphocytes and inflammatory markers. The researchers compared the collected data between patients who were sufficient to those who were deficient in Vitamin D levels.
They determined that patients over the age of 40 who were Vitamin D sufficient were 51.5% less likely to die from a COVID-19 infection than those who were deficient in the vitamin.
“Because Vitamin D deficiency and insufficiency is so widespread in children and adults in the United States and worldwide, especially in the winter months, it is prudent for everyone to take a vitamin D supplement to reduce risk of being infected and having complications from COVID-19,” Michael F. Holick, PhD, MD (above), told SciTechDaily. The Boston University School of Medicine professor and study author has been praising the health benefits of Vitamin D for years. He played a role in drafting national guidelines for the vitamin and also authored books that tout the advantages of Vitamin D, the importance of UV rays, and the biologic effects of light. (Photo copyright: Boston Herald.)
How Vitamin D Works and Why It’s So Important
In a fact sheet, the National Institutes of Health (NIH) recommend that adults between the ages of 19 and 70 take 15 micrograms (mcg) or 600 International Units (IU) of Vitamin D per day. Adults over the age of 70 should increase that amount to 20 mcg or 800 IUs per day.
According NBC News, Americans spent $936 million on supplements in 2017, which was nine times more than the previous decade. That article also stated that medical laboratory testing for Vitamin D levels have exponentially increased over the years. More than 10 million tests for Vitamin D levels were ordered for Medicare patients in 2016 at a cost of $365 million, which represents an increase of 547% since 2007. Currently, approximately one in four adults over the age of 60 in the US take Vitamin D supplements.
The NIH fact sheet notes that Vitamin D is a nutrient found in cells throughout the body and is needed for good health and to maintain strong bones. Individuals who are deficient in Vitamin D may develop soft, thin, brittle bones, as well as rickets in children and osteomalacia in adults. Vitamin D also helps the immune system fight off invading bacteria and viruses, helps nerves carry messages between the brain and other body parts, and helps muscles move. It can also play a role in warding off osteoporosis in older adults.
Very few foods naturally contain Vitamin D. The best dietary sources for the vitamin are fatty fish such as salmon, tuna, and mackerel, and foods fortified with Vitamin D, such as milks, some breakfast cereals, and yogurt. Being outside on sunny days is another way to obtain Vitamin D, as the body makes the vitamin when skin is directly exposed to the sun.
The Boston University study outlines the advantages of having sufficient Vitamin D levels, as well as how the vitamin may help ward off and possibly lessen the effects of infections like COVID-19, though those conclusions have been called into question.
Nevertheless, individuals who are deficient in the vitamin may want to take a supplement or get plenty of sunshine, just to be on the safe side. And clinical laboratory managers will want to keep in mind that over the years “the steady increase in physician and patient demand for Vitamin D tests has kept most clinical and pathology laboratories scrambling to maintain turnaround times and quality,” which Dark Daily reported in “Why Vitamin D Continues to Be the World’s Fastest-Growing Clinical Laboratory Test.”
In their letter, the Representatives wrote, “As you are aware, the recently enacted Paycheck Protection Program and Health Care Enhancement Act (PPPHCE Act) invests $25 billion in the [Public Health and Social Services Emergency Fund (PHSSEF)], including $11 billion for states, localities, territories, and tribes, to enhance all aspects of COVID-19 testing capacity. This funding is in addition to the funds already appropriated to the PHSSEF under the CARES Act.
“While laboratories are eligible, along with other providers, for these funds,” they continued, “there have been no federal funds specifically designated for the laboratories that have stepped up in this public health crisis and have made significant investments to expand access to COVID-19 testing despite 40-60 percent reductions in regular commercial volume due to the economic lockdowns.
“As laboratories work to maintain their investments in critical resources for testing platforms, reagents, swabs, and PPE, as well as hiring, training, and overtime pay for the laboratory workforce, we urge HHS to direct a portion of funding that has not already been allocated towards these efforts. These funds will ensure that labs can continue to rapidly scale up diagnostic and antibody testing, particularly for healthcare workers, first responders, and other Americans on the frontlines of this pandemic,” concluded the Representatives.
ACLA President Made Similar Plea for Direct Funding to Clinical Laboratories
“In order to deliver accurate, reliable results for patients at a national scale, we must allocate funding to support [clinical laboratories’] expanded efforts,” she said in a statement following an April 27 meeting at the White House.
In her letter, Khani wrote, “It is essential that HHS allocate $10 billion from the fund to support labs’ further expansion of testing capacity to fulfill the testing needs of all of the states and to protect the lives and livelihood of all Americans.
“Further,” she continued, “HHS should note that investing in the nation’s laboratories will not only enhance testing capacity in the short-term, but it also will allow the country to benefit from a robust testing infrastructure for the duration of the COVID-19 pandemic and beyond.”
President Trump signed H.R.266 into law on April 24. It includes $25 billion earmarked for research, development, validation, manufacturing, purchasing, administering, and expanding capacity for COVID-19 testing. According to the language of H.R.266, that includes, “tests for both active infection and prior exposure, including molecular, antigen, and serological tests, the manufacturing, procurement and distribution of tests, testing equipment and testing supplies, including personal protective equipment needed for administering tests, the development and validation of rapid, molecular point-of-care tests, and other tests, support for workforce, epidemiology, to scale up academic, commercial, public health, and hospital laboratories, to conduct surveillance and contact tracing, support development of COVID-19 testing plans, and other related activities related to COVID-19 testing.”
“As the demand for testing continues to grow, clinical laboratories need dedicated funding to plan for challenges that lie ahead. Strong federal coordination and leadership is essential, and we’re looking forward to working with HHS to ensure that laboratories have the resources necessary to continue to expand our role at the forefront of the nation’s response,” said Julie Khani (above), President of the American Clinical Laboratory Association (ACLA), in a press release following the June 8 letter sent to HHS by 30 members of Congress requesting funds from H.R.266 be sent directly to clinical laboratories. Khani will be speaking on federal policies now impacting clinical laboratories at the upcoming 25th annual Executive War College on Laboratory and Pathology Management in New Orleans on July 14-15. (Photo copyright: ACLA.)
Financial Struggles for Hospitals and Clinical Laboratories
This new round of stimulus funding comes at a time when many providers and clinical laboratories are struggling financially, despite the influx of COVID-19 patients.
“Across the country, laboratories have made significant investments to expand capacity, including purchasing new platforms, retraining staff, and managing the skyrocketing cost of supplies. To continue to make these investments and expand patient access to high-quality testing in every community, laboratories will need designated resources. Without sustainable funding, we cannot achieve sustainable testing,” said Khani in an ACLA statement.
As the COVID-19 coronavirus pandemic evolves, federal regulations, as well as emergency funding for COVID-19 testing that is provided by federal legislation, will evolve in unexpected ways. For that reason, clinical laboratory leaders will want to closely track announcements by such federal agencies as the Department of Health and Human Services, the Centers for Medicare and Medicaid Services, the Food and Drug Administration, the Centers for Disease Control and Prevention, and the Federal Emergency Management Administration as decisions are made about how to assign the $25 billion authorized in H.R.266 for “testing.”
