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Dutch Patient with Longest COVID-19 Case of 612 Days Had More than 50 SARS-CoV-2 Mutations Before He Died

Study of the 50 Omicron variants could lead to new approaches to clinical laboratory testing and medical treatments for long COVID

Patients infected with SARS-CoV-2 can usually expect the COVID-19 illness to subside within a couple of weeks. However, one Dutch patient remained infected with the coronavirus for 612 days and fought more than 50 mutations (aka, variants) before dying late last year of complications due to pre-existing conditions. This extreme case has given doctors, virologists, microbiologists, and clinical laboratories new insights into how the SARS-CoV-2 virus mutates and may lead to new treatments for long COVID.

According to Scientific American, when the 72-year-old male patient was admitted to the Amsterdam University Medical Center (Amsterdam UMC) in 2022 with the Omicron variant of SARS-CoV-2, he was also found to have myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN) overlap syndromes. Thus, the patient was determined to be immunocompromised.

“This was complicated by the development of a post-transplant lymphoma for which he received rituximab [a monoclonal antibody medication used to treat certain autoimmune diseases and cancers] that depletes all available B-cells, including those that normally produce the SARS-CoV-2 directed antibodies,” according to a press release.

The medication the patient was taking for his pre-existing conditions may have contributed to his body being unable to produce antibodies in response to three shots of the Moderna mRNA COVID vaccine he received.

Magda Vergouwe, MD, PhD candidate at the Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, who lead a study into the patient, theorized that some of the medications the patient was on for his pre-existing conditions could have destroyed healthy cells alongside the abnormal cancer-causing B cells the drugs were meant to target.

“This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals,” the researchers said prior to presenting their report about the case at a meeting of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in Barcelona, Spain, Time reported. “We emphasize the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections.”

“Chronic infections and viral evolution [are] commonly described in [the] literature, and there are other cases of immunocompromised patients who have had [COVID] infections for hundreds of days,” Magda Vergouwe, MD, PhD candidate (above), Center for Experimental and Molecular Medicine at Amsterdam UMC, told Scientific American. “But this is unique due to the extreme length of the infection … and with the virus staying in his body for so long, it was possible for mutations to just develop and develop and develop.” Microbiologists, virologists, and clinical laboratories involved in testing patients with long COVID may want to follow this story. (Photo copyright: LinkedIn.)

Risks to Immunocompromised Patients

Pre-existing conditions increase the risk factor for COVID-19 infections. A 2021 study published in the Journal of the American Board of Family Medicine (JABFM) titled, “Prevalence of Pre-existing Conditions among Community Health Center Patients with COVID-19,” found that about 61% of that study’s test group had a pre-existing condition prior to the outbreak of the COVID-19 pandemic.

When the Dutch man was admitted to Amsterdam UMC with common and serious COVID-19 symptoms, such as shortness of breath, a cough, and low blood oxygen levels, he was prescribed sotrovimab (a monoclonal antibody) along with other COVID treatments.

About a month after being admitted his COVID-19 symptoms decreased, so he was first discharged to a rehab facility and then finally to his home. However, he continued to test positive for the coronavirus and developed other infections that may have been complicated by the persistent case of COVID-19.

The Amsterdam UMC doctors emphasized that the man ultimately succumbed to his pre-existing conditions and not necessarily COVID-19.

“It’s important to note that in the end he did not die from his COVID-19,” Vergouwe told Scientific American. “But he did keep it with him for a very long period of time until then, and this is why we made sure to sample [the virus in his body] as much as we could.”

One in Five Adults Develop Long COVID

Long COVID does not necessarily indicate an active infection. However, in as many as one in five US adults COVID symptoms persist after the acute phase of the infection is over, according to a study published recently in JAMA Network Open titled, “Epidemiologic Features of Recovery from SARS-CoV-2 Infection.”

“In this cohort study, more than one in five adults did not recover within three months of SARS-CoV-2 infection. Recovery within three months was less likely in women and those with pre-existing cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave,” the JAMA authors wrote.

The origins of long COVID are not entirely clear, but according to the National Institutes of Health (NIH) it can develop when a patient is unable to sufficiently rest while battling off the initial virus. According to Vergouwe, the SARS-CoV-2 genome will always grow quicker when found in a patient with a compromised immune system.

Unique COVID-19 Mutations

More than 50 new mutations of the original Omicron variant were identified in the Dutch patient. According to Vergouwe, “while that number can sound shocking, mutations to the SARS-CoV-2 genome are expected to evolve more quickly in those who are immunocompromised (the average mutation rate of the virus is estimated to be two mutations per person per month),” Scientific American reported. “What does make these mutations unusual, she noted, is how their features differed vastly from mutations observed in other people with COVID. [Vergouwe] hypothesizes that the exceptional length of the individual’s infection, and his pre-existing conditions, allowed the virus to evolve extensively and uniquely.”

COVID-19 appears to be here to stay, and most clinical laboratory managers and pathologists understand why. As physicians continue to learn about the SARS-CoV-2 coronavirus, this is another example of how the knowledge about SARS-CoV-2 is growing as different individuals are infected with different variants of the virus.

—Ashley Croce

Related Information:

Longest-Ever COVID Infection Lasted More than 600 Days

COVID Patient’s Infection Lasts Record 613 Days—and Accumulated Over 50 Mutations

72-Year-Old Patient Had COVID for Record 613 Days, Accumulated over 50 Mutations from Virus Before It Killed Him

Prevalence of Preexisting Conditions among Community Health Center Patients with COVID-19: Implications for the Patient Protection and Affordable Care Act

The Risk Factors for Long COVID Have Finally Been Revealed

Prevalence of Pre-existing Conditions among Community Health Center Patients with COVID-19

Epidemiologic Features of Recovery from SARS-CoV-2 Infection

Genetic Testing of Wastewater Now Common in Detecting New Strains of COVID-19 and Other Infectious Diseases

History of the Clinical Laboratory Critical Values Reporting System

Development of the Critical Values system redefined what STAT means in clinical laboratory testing turnaround times

Where did the concept of critical values and having clinical laboratories report them to referring physicians originate? How did the concept blossom into a standard practice in laboratory medicine? Given the importance of critical values, a lookback into how this aspect of laboratory medicine was developed is helpful to understand how and why this has become an essential element in the practice of medicine and an opportunity for labs to add value in patient care.

According to Stanford Medicine, critical/panic values are defined as “values that are outside the normal range to a degree that may constitute an immediate health risk to the individual or require immediate action on the part of the ordering physician.”

In an article he penned for the National Medical Journal of India, George Lundberg, MD, Editor-at-Large at Medscape, states that the practice of reporting critical values originated with a case that occurred in 1969 at the Los Angeles County-University of Southern California Medical Center. Lundberg is also Editor-in-Chief at Cancer Commons, President and Chair of the Board of Directors of the Lundberg Institute, and a clinical professor of pathology at Northwestern University.

What you’ll read below is an insider’s account of the “birth of critical values reporting.”

According to Lundberg, an unaccompanied man was brought to the hospital in a coma and an examination revealed a laceration to his scalp. The patient was admitted to the neurosurgical unit where clinical laboratory tests were performed, including a complete blood count (CBC) analysis, urinalysis, and serum electrolytes. All the test results came back normal except the patient’s serum glucose (blood sugar level) which was 6 mg% in concentration.

“The hard-copy laboratory results were returned to the ward of origin within two hours of receipt of the specimens in the laboratory. However, the results were not noticed by the house officers who were busy with several other seriously ill patients. Ward personnel also failed to communicate the lab results to the responsible physicians,” Lundberg wrote.

When hospital staff did finally notice the test result the next morning glucose was immediately administered to the patient, but it was too late to prevent irreversible brain damage. The man soon passed away.

Following this incident, the hospital developed a “Critical Value Recognition and Reporting System.” The system generated new numbers that were termed “Panic Values.” 

However, “critics complained that good doctors should never panic, so the name was changed to Critical Values,” Lundberg explained.

When any of these critical test values were out of the norm, “we required the responsible laboratory person to quickly verify the result and use the telephone (long before laboratory computers) to personally notify a responsible individual (no messages left) who agreed to find a physician who could quickly act on the result. All was documented with times and names,” he wrote. 

“We understand that when a physician wants something, he/she wants it, no matter what. Well, in this patient-focused approach, the physician cannot have it, except as offered by the patient-focused approach, based on TAT [turnaround times of clinical laboratory tests],” wrote George Lundberg, MD (above), President and Chair of the Board of Directors of the Lundberg Institute, and Clinical Professor of Pathology at Northwestern University in an article he penned for the National Medical Journal of India (Photo copyright: Dark Intelligence Group. Shows Dr. Lundberg in 2011 addressing the Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management.)

New Clinical Laboratory Standards

Recognition of the urgency to adopt new hospital standards related to certain clinical laboratory test results came swiftly. In 1972, Lundberg was invited to publish an article explaining the new Critical Value Recognition and Reporting System in Medical Laboratory Observer

“Within weeks, laboratories all over the USA adopted their own version of the system,” Lundberg wrote in his National Medical Journal of India (NMJI) article. “The test chosen, and critical values, were established by each medical staff. … A critical value system quickly became standard of practice as required by the College of American Pathologists (CAP) Laboratory Accreditation Program and the Joint Commission on Accreditation of Hospitals.”

According to Lundberg, “most laboratory tests that are done do not need to be done; the results are either negative, normal, or show no change from a prior result. But some are crucial.”

The original set of Critical Values included the following testing results:

The list of values were later expanded to include “vital values.” These values describe lab results for which “action” is important, but where timing is less urgent. Examples of vital values include:

STAT Lab Orders Redefined

Lundberg and his colleagues went on to redefine what constitutes a laboratory test and what renders a test successful. They discussed laboratory procedures with committees of clinicians, lab personnel and patients, and reorganized hematology, chemistry, and toxicology based on the turnaround time (TAT) of tests.

“We ‘started the clock’—any and all days/times 24×7—when a specimen arrived at some place within the laboratory, and stopped the clock when a final result was available somewhere in the laboratory,” Lundberg wrote in NMJI. “We categorized all tests as: less than one hour, less than four hours, less than 24 hours, and more than 24 hours, guaranteed, 24×7. As a trade-off, we abolished the concept of ‘STAT’ orders … NO EXCEPTIONS. The rationale of each TAT was the speed with which a result was needed to render proper medical care that mattered to the welfare of the patient, and, of course, that was technically possible.”

Since then, very little has changed for the Critical Values System over the past 50 years. The majority of values added have fallen under the “Vital” category and not the “Critical” category. Today, most health systems and clinical laboratories create their own internal processes and procedures regarding which values need to be reported immediately (critical), which values are not urgent (vital), and how those results should be handled.

—JP Schlingman

Related Information:

The Origin and Evolution of Critical Laboratory Values

Critical Values

Critical Laboratory Values Communication: Summary Recommendations from Available Guidelines

Researchers Find That Antibiotic-Resistant Bacteria Can Persist in the Body for Years

Study results from Switzerland come as clinical laboratory scientists seek new ways to tackle the problem of antimicrobial resistance in hospitals

Microbiologists and clinical laboratory scientists engaged in the fight against antibiotic-resistant (aka, antimicrobial resistant) bacteria will be interested in a recent study conducted at the University of Basel and University Hospital Basel in Switzerland. The epidemiologists involved in the study discovered that some of these so-called “superbugs” can remain in the body for as long as nine years continuing to infect the host and others.

The researchers wanted to see how two species of drug-resistant bacteria—K. pneumoniae and E. coli—changed over time in the body, according to a press release from the university. They analyzed samples of the bacteria collected from patients who were admitted to the hospital over a 10-year period, focusing on older individuals with pre-existing conditions. They found that K. pneumoniae persisted for up to 4.5 years (1,704 days) and E. coli persisted for up to nine years (3,376 days).

“These patients not only repeatedly become ill themselves, but they also act as a source of infection for other people—a reservoir for these pathogens,” said Lisandra Aguilar-Bultet, PhD, the study’s lead author, in the press release.

“This is crucial information for choosing a treatment,” explained Sarah Tschudin Sutter, MD, Head of the Division of Infectious Diseases and Hospital Epidemiology, and of the Division of Hospital Epidemiology, who specializes in hospital-acquired infections and drug-resistant pathogens. Sutter led the Basel University study.

The researchers published their findings in the journal Nature Communications titled, “Within-Host Genetic Diversity of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales in Long-Term Colonized Patients.”

“The issue is that when patients have infections with these drug-resistant bacteria, they can still carry that organism in or on their bodies even after treatment,” said epidemiologist Maroya Spalding Walters, MD (above), who leads the Antimicrobial Resistance Team in the Division of Healthcare Quality Promotion at the federal Centers for Disease Control and Prevention (CDC). “They don’t show any signs or symptoms of illness, but they can get infections again, and they can also transmit the bacteria to other people.” Clinical laboratories working with microbiologists on antibiotic resistance will want to follow the research conducted into these deadly pathogens. (Photo copyright: Centers for Disease Control and Prevention.)

COVID-19 Pandemic Increased Antibiotic Resistance

The Basel researchers looked at 76 K. pneumoniae isolates recovered from 19 patients and 284 E. coli isolates taken from 61 patients, all between 2008 and 2018. The study was limited to patients in which the bacterial strains were detected from at least two consecutive screenings on admission to the hospital.

“DNA analysis indicates that the bacteria initially adapt quite quickly to the conditions in the colonized parts of the body, but undergo few genetic changes thereafter,” the Basel University press release states.

The researchers also discovered that some of the samples, including those from different species, had identical mechanisms of drug resistance, suggesting that the bacteria transmitted mobile genetic elements such as plasmids to each other.

One limitation of the study, the authors acknowledged, was that they could not assess the patients’ exposure to antibiotics.

Meanwhile, recent data from the World Health Organization (WHO) suggests that the COVID-19 pandemic might have exacerbated the challenges of antibiotic resistance. Even though COVID-19 is a viral infection, WHO scientists found that high percentages of patients hospitalized with the disease between 2020 and 2023 received antibiotics.

“While only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring antibiotics, three out of four or some 75% of patients have been treated with antibiotics ‘just in case’ they help,” the WHO stated in a press release.

WHO uses an antibiotic categorization system known as AWaRe (Access, Watch, Reserve) to classify antibiotics based on risk of resistance. The most frequently prescribed antibiotics were in the “Watch” group, indicating that they are “more prone to be a target of antibiotic resistance and thus prioritized as targets of stewardship programs and monitoring.”

“When a patient requires antibiotics, the benefits often outweigh the risks associated with side effects or antibiotic resistance,” said Silvia Bertagnolio, MD, Unit Head in the Antimicrobial resistance (AMR) Division at the WHO in the press release. “However, when they are unnecessary, they offer no benefit while posing risks, and their use contributes to the emergence and spread of antimicrobial resistance.”

Citing research from the National Institutes of Health (NIH), NPR reported that in the US, hospital-acquired antibiotic-resistant infections increased 32% during the pandemic compared with data from just before the outbreak.

“While that number has dropped, it still hasn’t returned to pre-pandemic levels,” NPR noted.

Search for Better Antimicrobials

In “Drug-Resistant Bacteria Are Killing More and More Humans. We Need New Weapons,” Vox reported that scientists around the world are researching innovative ways to speed development of new antimicrobial treatments.

One such scientist is César de la Fuente, PhD, Presidential Assistant Professor at University of Pennsylvania, whose research team developed an artificial intelligence (AI) system that can look at molecules from the natural world and predict which ones have therapeutic potential.

The UPenn researchers have already developed an antimicrobial treatment derived from guava plants that has proved effective in mice, Vox reported. They’ve also trained an AI model to scan the proteomes of extinct organisms.

“The AI identified peptides from the woolly mammoth and the ancient sea cow, among other ancient animals, as promising candidates,” Vox noted. These, too, showed antimicrobial properties in tests on mice.

These findings can be used by clinical laboratories and microbiologists in their work with hospital infection control teams to better identify patients with antibiotic resistant strains of bacteria who, after discharge, may show up at the hospital months or years later.

—Stephen Beale

Related Information:

Resistant Bacteria Can Remain in The Body for Years

‘Superbugs’ Can Linger in the Body for Years, Potentially Spreading Antibiotic Resistance

Superbug Crisis Threatens to Kill 10 Million Per Year by 2050. Scientists May Have a Solution

Drug-Resistant Bacteria Are Killing More and More Humans. We Need New Weapons.

How the Pandemic Gave Power to Superbugs

WHO Reports Widespread Overuse of Antibiotics in Patients Hospitalized with COVID-19

Yale University’s Mobile Clinical Laboratory Provides Free Medical Tests to Underserved Communities in Connecticut

Clinical laboratories nationwide could follow Yale’s example and enact programs to bring much needed lab services to traditionally underserved communities

Ever since the COVID-19 pandemic drove up demand for telehealth medical services, mobile clinical laboratories have grown in popularity as well, especially among residents of remote and traditionally underserved communities. Now, several divisions of Yale University are getting in on the trend.

In April, Yale Pathology Labs (YPL), the Yale Department of Pathology at Yale School of Medicine (YSM), and Yale School of Public Health (YSPH) unveiled their new Laboratory-in-a-Van program with plans to bring free clinical laboratory services to the public in the communities where they live, a YSPH news release announced. 

“Using a van retrofitted with laboratory-grade diagnostic equipment, the mobile clinic will employ SalivaDirect—a saliva-based COVID-19 PCR test developed at YSPH—to facilitate on-site testing with a turnaround time of two to three hours,” Yale Daily News reported.

Funded by a federal grant, the initial goal was to provide 400 free COVID-19 tests, but the program has exceeded that number. By April 10, the mobile lab had been deployed more than 60 times, appearing at events and pop-up sites throughout various communities in Connecticut, including regular stops at the WHEAT Food Pantry of West Haven.

“[The clinical laboratory-in-a-van] is a brilliant way to reduce the barriers to testing, instead taking the lab to communities who may be less likely—or unable—to access the necessary clinic or labs,” microbiologist Anne Wyllie, PhD, a research scientist who helped develop the PCR test deployed by the mobile lab told Yale Daily News. Wyllie works in the Department of Epidemiology of Microbial Diseases at Yale School of Public Health. “We are actively working with our community partners to identify how we can best serve their communities,” she added. (Photo copyright: Yale School of Medicine.)

Mobile Lab’s Capabilities

Collecting samples, processing, and delivering same-day COVID-19 results was the initial goal but that plan has expanded, Yale School of Medicine noted in a news release

“Same-day onsite delivery of test results is an added benefit for communities and individuals without access to Wi-Fi or the ability to receive private health information electronically,” Yale added. 

The mobile van is staffed with trained clinical laboratory technicians as well as community health navigators who provide both healthcare information and proper follow-up connections as needed for patients who receive positive COVID-19 results. The van runs off power from outdoor electrical outlets at each location and currently serves historically underserved populations in Hartford, Middlesex, Fairfield, New Haven, and New London counties, Yale noted.

“The van allows us to bring our services, as well as healthcare information, directly to communities where they are needed,” said Angelique Levi, MD, Associate Professor, Vice Chair and Director of Pathology Reference Services, and CLIA Laboratory Medical Director in the Department of Pathology at Yale University School of Medicine in a news release.

Launch of a High Complexity Molecular Lab on Wheels

YPL and YSPH collaborated to make the mobile lab a reality. YSPH created the saliva-based COVID-19 test and YPL “provided clinical validation necessary to get the testing method ready for emergency use authorization by the US Food and Drug Administration,” Yale noted.

“YPL recognized the need to be closer to the front lines of patient care and that retrofitting a fully licensed, high complexity molecular laboratory into a consumer-sized van was the right next step,” Chen Liu, MD, PhD, Chair of the Department of Pathology at Yale School of Medicine, noted in a Yale news release. This “gives us options to efficiently deliver accurate diagnostic information when and where it’s needed,” he added.

Throughout the COVID-19 pandemic, the Connecticut Department of Public Health, the City of New Haven, and various community organizations partnered with YPL, YSPH, and the SalivaDirect team to offer free SARS-CoV-2 testing to the public at two different sites in New Haven.

Principal investigators Levi and microbiologist Anne Wyllie, PhD, who helped develop the PCR test deployed by the mobile, lab led the Yale lab-in-a-van research project.

Flambeau Diagnostics, a biomedical company that specializing in mobile lab testing, worked with the Yale team to design and implement the mobile lab van.

“According to Wyllie, the new YSPH and YPL initiative utilizes one of the former Flambeau vans that had been retrofitted for clinical testing,” a Yale news release noted.

Kat Fajardo, Laboratory Manager at Yale University, added custom pieces of equipment to ensure seamless PCR testing. One was a Magnetic Induction Cycler (Mic) measuring only six by six inches. The Mic allowed for measurement of 46 biological specimens, while it’s diminutive size freed up space on the van’s countertop. This allowed lab techs to process specimens concurrently while also providing COVID-19 testing, according to a Yale news release.

Additionally, the van has a Myra portable robotic liquid handler which is “designed to automate the process of moving clinical specimens between vials,” the news release notes.

“What we wanted to do is run high complexity testing in the van, with a reduced timeframe, and then be able to get the results out to the patients as soon as we possibly could,” Fajardo stated.

Exploring the Mobile Laboratory’s Potential

According to a news release, YPL and YSPH consult with community partners to select locations for the mobile lab to visit. These partners include:

Although the van was initially used to provide SalivaDirect COVID-19 testing to vulnerable populations, YPL is working with its partners in those communities to identify other testing needs beyond COVID.

The Yale team is considering additional offerings and support such as the addition of a social worker as well as expanding lung health awareness beyond COVID-19 to other respiratory diseases. Also under consideration:

  • Health screenings such as for glucose levels,
  • Blood pressure checks,
  • Vaccinations including for COVID-19 and Hepatitis B, and
  • Health education and materials for harm reduction and STI prevention, a Yale news release noted. 

Yale’s Laboratory-in-a-Van program is a consumer-facing effort that is bringing much needed clinical lab services to traditionally underserved communities in Connecticut. Clinical laboratories throughout the nation could do the same with remote or homebound patients who cannot reach critical care.

—Kristin Althea O’Connor

Related Information:

High-Tech Mobile Lab-in-a-Van Will Bring Needed Testing to Underserved Communities

Yale Pathology Labs Mobile Lab Provides over 400 Free Tests to Community

Yale Pathology Labs to Serve Vulnerable Populations with New Mobile Testing Van

YSPH and YPL launch Laboratory-in-a-Van program

Endocrine Society Releases New Guidelines Advising Physicians to Not Screen for Vitamin D, which Could Affect Test Referrals to Clinical Laboratories

New guidelines also advise people to limit their vitamin D supplementation to recommended daily doses

Clinical laboratories may eventually receive fewer doctors’ orders for vitamin D testing thanks to new guidelines released by the Endocrine Society. The new Clinical Practice Guideline advises against “unnecessary testing for vitamin D levels.” It also urges healthy people, and those 75-years of age or younger, to avoid taking the vitamin at levels above the daily recommended amounts, according to a news release.

The Society shared its recommendations at its annual meeting and in the Journal of Clinical Endocrinology and Metabolism titled, “Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.”

Even though the Endocrine Society does recommend vitamin D supplements for certain groups, it advises individuals to hold off on routine testing. That’s because there appears to be uncertainty among ordering clinicians about what to do for patients based on their vitamin D test results.

“When clinicians measure vitamin D, they’re forced to decide what to do about it. That’s where questions about the levels come in. And that’s a big problem. So, what this panel is saying is ‘Don’t screen,’” Clifford Rosen, MD, Director of Clinical and Translational Research and Senior Scientist, Maine Medical Center Research Institute at the University of Maine, told Medscape Medical News.

“We have no data that there’s anything about screening that allows us to improve quality of life. Screening is probably not worthwhile in any age group,” he added.

“This guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them,” the author of the Endocrine Society guideline, Anastassios G. Pittas, MD (above), Professor of Medicine at Tufts University School of Medicine in Boston, told Medscape Medical News. This new guideline could result in doctors ordering fewer vitamin D tests from clinical laboratories. (Photo copyright: Tufts University.)

Vitamin D Screening Not Recommended for Certain Groups

The Endocrine Society’s new clinical guidelines advise healthy adults under 75 years of age to refrain from taking vitamin D supplements that exceed US Institute of Medicine—now the National Academy of Medicine (NAM)—recommendations.

Additionally, these updated guidelines:

  • Recommend vitamin D supplements at levels above NAM recommendations to help lower risks faced by children 18 years and younger, adults 75 and older, pregnant women, and people with prediabetes.
  • Suggest daily, lower-dose vitamin D (instead of non-daily, higher-dose of the vitamin) for people 50 years and older who have “indications for vitamin D supplementation or treatment.”
  • Advise “against routine testing for 25-hydroxyvitamin D [aka, calcifediol] levels” in all the above groups “since outcome-specific benefits based on these levels have not been identified. This includes 25-hyrdoxyvitamin D screening in people with dark complexion or obesity.”

One exception to the guideline applies to people with already established osteoporosis, according to the guideline’s author endocrinologist Anastassios G. Pittas, MD, Chief of Endocrinology, Diabetes and Metabolism; Co-Director, Tuft’s Diabetes and Lipid Center; and Professor of Medicine at Tufts University School of Medicine in Boston.

Vitamin D’s Link to Disease Studied

During a panel discussion at the Endocrine Society’s annual meeting, members acknowledged that many studies have shown relationships between serum concentrations of 25-hydroxy vitamin D (25(OH)D) and physical disorders including those of musculoskeletal, metabolic, and cardiovascular systems. Still, they questioned the link of vitamin D supplementation and testing with disease prevention.

“There is paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases. … What we really need are large-scale clinical trials and biomarkers so we can predict disease outcome before it happens,” said Panel Chair Marie Demay, MD, Endocrinologist, Massachusetts General Hospital, and Professor of Medicine, Harvard Medical School, Boston, Medscape Medical News reported.

Meanwhile, in their Journal of Clinical Endocrinology and Metabolism paper, the researchers note that use of supplements (1,000 IU or more per day) increased from 0.3% to 18.2%, according to the National Health and Nutrition Examination Survey (NHANES) conducted by the National Center for Health Statistics (NCHS), CDC, for the years 1999-2000 and 2013-2014.

“The use of 25(OH)D testing in clinical practice has also been increasing; however, the cost effectiveness of widespread testing has been questioned, especially given the uncertainty surrounding the optimal level of 25(OH)D required to prevent disease,” the authors wrote.

“Thus, the panel suggests against routine 25(OH)D testing in all populations considered,” the researchers stated at the Endocrine Society annual meeting.

Other Groups Weigh-in on Vitamin D Testing

Pathologists and medical laboratory leaders may recall the explosion in vitamin D testing starting about 20 years ago. Vitamin D testing reimbursed by Medicare Part B “increased 83-fold” during the years 2000 to 2010, according to data cited in an analysis by the American Academy of Family Physicians (AAFP).

“Screening for vitamin D deficiency leads to hundreds of millions of dollars of waste in testing costs annually,” the AAFP noted in an editorial on the organization’s website titled, “Vitamin D Screening and Supplementation in Primary Care: Time to Curb Our Enthusiasm.”

Also, the US Preventive Services Task Force (USPSTF) said in a statement that there is not enough information to “recommend for or against” testing for vitamin D deficiency.

“No organization recommends population-based screening for vitamin D deficiency, and the American Society for Clinical Pathology recommends against it,” the USPSTF noted.

Clinical Laboratories Can Get the Word Out

The vitamin D debate has been going on for a while. And the latest guidance from the Endocrine Society may cause physicians and patients to stop ordering vitamin D tests as part of annual physicals or in routine screenings.

Medical laboratories can provide value by ensuring physicians and patients have the latest information about vitamin D test orders, reports, and interpretation.

—Donna Marie Pocius

Related Information:

Endocrine Society Recommends Healthy Adults Take the Recommended Daily Allowance of Vitamin D

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline

Don’t Screen for Vitamin D: New Endo Society Guideline

Institute of Medicine Recommendations Vitamin D

Vitamin D Screening and Supplementation in Primary Care: Time to Curb Our Enthusiasm

US Preventive Services Task Force Recommendation Vitamin D Deficiency Screening

FDA Grants Marketing Authorization to First Ever AI-Powered SaMD Diagnostic Tool for Sepsis That Shares Patient’s Risk within 24 Hours and Works with EHRs

Infection control teams and clinical laboratory managers may want to look at this new product designed to improve the diagnosis and treatment of sepsis

Accurate and fast diagnosis of sepsis for patients arriving in emergency departments is the goal of a new product that was just cleared by the federal Food and Drug Administration (FDA). It is also the newest example of how artificial intelligence (AI) continues to find its way into pathology and clinical laboratory medicine.

Sepsis is one of the deadliest killers in US hospitals. That is why there is interest in the recent action by the FDA to grant marketing authorization for an AI-powered sepsis detection software through the agency’s De Novo Classification Request. The DNCR “provides a marketing pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device,” the FDA’s website states.

Developed by Chicago-based Prenosis, the Sepsis ImmunoScore is an AI and machine learning (ML) Software as a Medical Device (SaMD) used to “guide rapid diagnosis and prediction of sepsis” within 24 hours of the patient’s presentation in an emergency department or hospital, according to a company news release.

In a separate statement, Prenosis announced a commercial distribution deal with Roche, Basel, Switzerland, as well as the SaMD’s availability on Roche’s navify Algorithm Suite (a digital library of medical algorithms).

Unlike a single analyte assay that is run in a clinical laboratory, Prenosis’ AI/ML software uses 22 diagnostic and predictive parameters, along with ML algorithms, to analyze data and produce a clinically actionable answer on sepsis.

It is important for clinical laboratory managers and pathologists to recognize that this diagnostic approach to sepsis brings together a number of data points commonly found in a patient’s electronic health record (EHR), some of which the lab generated and others the lab did not generate.

“Sepsis is a serious and sometimes deadly complication. Technologies developed to help prevent this condition have the potential to provide a significant benefit to patients,” said Jeff Shuren, MD, JD, Director of the FDA’s Center for Devices and Radiological Health, in a statement. “The FDA’s authorization of the Prenosis Sepsis ImmunoScore software establishes specific premarket and post-market requirements for this device type.” Clinical laboratory EHRs contain some of the data points Prenosis’ diagnostic software uses. (Photo copyright: US Food and Drug Administration.)  

How it Works

To assist doctors diagnose sepsis, the ImmunoScore software is first integrated into the patient’s hospital EHR. From there, it leverages 22 parameters including:

Instead of requiring a doctor or nurse to look at each parameter separately, the SaMD tool uses AI “to evaluate all those markers at once”, CNBC noted. It then produces a risk score and four discrete risk stratification categories (low, medium, high, and very high) which correlate to “a patient’s risk of deterioration” represented by:

  • Hospital length of stay.
  • In-hospital mortality.
  • Intensive care unit transfer within 24 hours.
  • Vasopressor use within 24 hours.
  • Need for mechanical ventilation within 24 hours.

By sharing these details—a number from one to 100 for each of the 22 diagnostic and predictive parameters—Sepsis ImmunoScore helps doctors determine which will likely contribute most to the patient’s risk for developing sepsis, MedTech Dive reported.

“A lot of clinicians don’t trust AI products for multiple reasons. We are trying very hard to counter that skepticism by making a tool that was validated by the FDA first, and then the second piece is we’re not trying to replace the clinician,” Bobby Reddy Jr., PhD, Prenosis co-founder and CEO, told MedTech Dive.

Big Biobank and Blood Sample Data

Prenosis, which says its goal is the “enabling [of] precision medicine in acute care” developed Sepsis ImmunoScore using the company’s own biobank and a dataset of more than 100,000 blood samples from more than 25,000 patients.

AI algorithms drew on this biological/clinical dataset—the largest in the world for acute care patients suspected of having serious infections, according to Prenosis—to “elucidate patterns in rapid immune response.”

Carle Foundation Hospital, Urbana, Ill., is one of three Illinois hospitals that helped build the biobank and dataset used by Prenosis, according to a Carle news release.

“It does not work without data, and the data started at Carle,” said critical care specialist Karen White, MD, PhD, Carle Foundation Hospital, St. Louis, MO, in the news release.  “The project involved a large number of physicians, research staff, and internal medicine residents at Carle who helped recruit patients, collect data, and samples,” she said.

Opportunity for Clinical Laboratories

Sepsis is a life-threatening condition based on an “extreme response to an infection” that affects nearly 1.7 million adults in the US each year and is responsible for 350,000 deaths, according to US Centers for Disease Control and Prevention (CDC) data. 

A non-invasive diagnostic tool like Sepsis ImmunoScore will be a boon to emergency physicians and the patients they treat. Now that the FDA has authorized the SaMD diagnostic tool to go to market, it may not be long before physicians can use the information it produces to save lives.

Clinical laboratory managers inspired by the development of Sepsis ImmunoScore may want to look for similar ways they can take certain lab test results and combine them with other data in an EHR to create intelligence that physicians can use to better treat their patients. The way forward in laboratory medicine will be combining lab test results with other relevant sets of data to create clinically actionable intelligence for physicians, patients, and payers.

—Donna Marie Pocius

Related Information:

Prenosis Announces FDA De Novo Marketing Authorization of the Sepsis ImmunoScore  

Prenosis Announces Commercial Distribution Collaboration with Roche for Sepsis ImmunoScore

FDA Authorizes Prenosis Software as First AI Tool That Can Diagnose Sepsis

FDA Round-Up April 5, 2024

FDA Grants De Novo Clearance to AI Tool for Detecting Sepsis

New AI Tool for Sepsis Diagnosis Gets its Start to Research at Carle

An AI Tool to Stop Sepsis