Clinical laboratory executives and pathology leaders may want to develop strategies for supporting the growing numbers of at-home screening and diagnostic test users
Findings of a national poll conducted by the University of Michigan (U-M) exploring consumers’ purchases suggests seniors are becoming more comfortable with ordering and using at-home medical testing. Their choice of tests and opinions may be of interest to clinical laboratory executives, pathologists, and primary care physicians considering programs to support self-test purchasers.
The researchers found that 48% of adults, ages 50 to 80, purchased at least one at-home medical test, and that 91% of the buyers indicated intentions to purchase another test in the future, according to a U-M news release.
In their paper, they note that “validity, reliability, and utility of at-home tests is often uncertain.” Further, understanding and responding to test results—especially since caregivers may not have ordered them—could lead to “a range of unintended consequences,” they wrote.
“As a primary care doctor, I would want to know why my patient chose to take an at-home test that I didn’t order for them. We also need to understand in greater detail why folks use at-home tests instead of traditional means, beyond convenience,” said the U-M study’s lead author Joshua Rager, MD, a research scientist at William M. Tierney Center for Health Services Research at Regenstrief Institute, who is now an assistant professor of medicine, Indiana University, in a news release. The findings of the U-M study will be of interest to clinical laboratory executives and pathology leaders. (Photo copyright: Regenstrief Institute.)
Free COVID-19 Tests Ignite At-Home Testing
In their Journal of Health Care paper, the U-M researchers speculate that curiosity in at-home testing may have been propelled by the offer of free COVID-19 tests by the US government starting in 2021 during the pandemic.
They also noted the different ways at-home test kits are performed by healthcare consumers. Some, such as COVID-19 rapid antigen tests, return results to users in a few moments similar to pregnancy tests. Others involve self-collecting specimens, such as a stool sample, then sending the specimen to a clinical laboratory for analysis and results reporting to physicians.
Of those older adults who participated in U-M’s National Poll on Healthy Aging study, the following bought at-home medical tests online or from pharmacies and supermarkets, according to U-M’s paper:
As to perceptions of at-home medical testing by users, when polled on their test experience, the surveyed seniors reported the following:
75.1% perceived at-home medical tests to be more convenient than conventional medical tests.
59.9% believe the tests “can be trusted to give reliable results.”
54.8% believe the tests “are regulated by government.”
66% called them a “good value.”
93.6% indicated results “should be discussed with my doctor.”
Inconsistency in how people shared test results with their healthcare providers was a concern voiced by the researchers.
“While nearly all patients who had bought an at-home cancer screening test shared the results with their primary care provider, only about half of those who tested for an infection other than COVID-19 had. This could have important clinical implications,” the researchers wrote in their paper.
Confusion over Government Regulation
The U-M study also revealed consumer misunderstanding about government regulation of at-home clinical laboratory tests purchased over-the-counter.
The US Food and Drug Administration (FDA) cleared “some diagnostic at-home tests for over-the counter use. But many tests on the market are unregulated or under-regulated,” the authors wrote, adding, “Our results suggest, however, that patients generally believe at-home tests are regulated by government, but a substantial minority did not, which may reflect public confusion in how at-home testing is regulated.”
Women, College-Educated Buy More At-Home Tests
Purchase of at-home tests varies among groups, as follows, the news release noted:
56% and 61% of older adults with a college degree or household income above $100,000, respectively, were “much more likely” to buy at-home tests than people in other income and education brackets.
87% of women would buy at-home tests again compared with 76% of men.
89% of college-educated people would purchase the tests again, compared with 78% of people with high school educations or less.
Future U-M research may explore consumers’ awareness/understanding concerning federal regulations of at-home testing, Rager noted.
“At-home tests could be used to address disparities in access to care. We hope these findings will inform regulators and policymakers and spark future research on this topic,” he said in the news release.
The U-M Institute for Healthcare Policy and Innovation survey results confirm that the country’s senior generations are becoming comfortable with at-home and self-testing options. As Dark Daily has previously suggested, clinical laboratories may want to develop service offerings and a strategy for supporting patients who want to perform their own lab tests at home.
The NIH’s Researching COVID to Enhance Recovery (RECOVER) Initiative used a cohort study of more than 10,000 individuals with and without previous COVID-19 diagnoses and compared samples using 25 common laboratory tests in hopes a useful biomarker could be identified. They were unsuccessful.
Long COVID—or PASC—is an umbrella term for those with persistent post-COVID infection symptoms that negatively impact quality of life. Though it affects millions worldwide and has been called a major public health burden, the NIH/Langone study scientists noted one glaring problem: PASC is defined differently in the major tests they studied. This makes consistent diagnoses difficult.
The study brought to light possible roadblocks that prevented biomarker identification.
“This study is an important step toward defining long COVID beyond any one individual symptom,” said study author Leora Horwitz, MD (above), director of the Center for Healthcare Innovation and Delivery Science and co-principal investigator for the RECOVER CSC at NYU Langone, in a Langone Health news release. “This definition—which may evolve over time—will serve as a critical foundation for scientific discovery and treatment design.” In the future, clinical laboratories may be tasked with finding combinations of routine and reference tests that, together, enable a more precise and earlier diagnosis of long COVID. (Photo copyright: Yale School of Medicine.)
NIH/Langone Study Details
“The study … examined 25 routinely used and standardized laboratory tests chosen based on availability across institutions, prior literature, and clinical experience. These tests were conducted prospectively in laboratories that are certified by the Clinical Laboratory Improvement Amendments (CLIA). The samples were collected from 10,094 RECOVER-Adult participants, representing a diverse cohort from all over the US,” Inside Precision Medicine reported.
However, the scientists found no clinical laboratory “value” among the 25 tests examined that “reliably indicate previous infection, PASC, or the particular cluster type of PASC,” Inside Precision Medicine noted, adding that “Although some minor differences in the results of specific laboratory tests attempted to differentiate between individuals with and without a history of infection, these findings were generally clinically meaningless.”
“In a cohort study of more than 10,000 participants with and without prior SARS-CoV-2 infection, we found no evidence that any of 25 routine clinical laboratory values provide a reliable biomarker of prior infection, PASC, or the specific type of PASC cluster. … Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC,” the study authors wrote in Annals of Internal Medicine.
In addition to a vague definition of PASC, the NIH/Langone researchers noted a few other potential problems identifying a biomarker from the research.
“Use of only selected biomarkers, choice of comparison groups, if any (people who have recovered from PASC or healthy control participants); duration of symptoms; types of symptoms or phenotypes; and patient population features, such as sex, age, race, vaccination status, comorbidities, and severity of initial infection,” could be a cause for ambiguous results, the scientists wrote.
Future Research
“Understanding the basic biological underpinnings of persistent symptoms after SARS-CoV-2 infection will likely require a rigorous focus on investigations beyond routine clinical laboratory studies (for example, transcriptomics, proteomics, metabolomics) to identify novel biomarkers,” the study authors wrote in Annals of Internal Medicine.
“Our challenge is to discover biomarkers that can help us quickly and accurately diagnose long COVID to ensure people struggling with this disease receive the most appropriate care as soon as possible,” said David Goff, MD, PhD, director of the division of cardiovascular sciences at the NIH’s National Heart, Lung, and Blood Institute, in an NHLBI news release. “Long COVID symptoms can prevent someone from returning to work or school, and may even make everyday tasks a burden, so the ability for rapid diagnosis is key.”
“Approximately one in 20 US adults reported persisting symptoms after COVID-19 in June 2024, with 1.4% reporting significant limitations,” the NIH/Langone scientists wrote in their published study.
Astute clinical laboratory scientists will recognize this as possible future diagnostic testing. There is no shortage of need.
Shortage could disrupt the ability of clinical laboratories in hospitals and health systems to run certain tests for bloodstream infections
US clinical laboratories may soon experience a “disruption of availability” of BACTEC blood culture media bottles distributed by Becton Dickinson (BD). That’s according to the federal Centers for Disease Control and Prevention (CDC) which issued a Health Alert Network (HAN) Health Advisory to all clinical laboratory professionals, healthcare providers and facility administrators, and other stakeholders warning of the potential shortfall of critical testing supplies.
“This shortage has the potential to disrupt patient care by leading to delays in diagnosis, misdiagnosis, or other challenges in the clinical management of patients with certain infectious diseases,” the CDC stated in the health advisory.
The CDC advises healthcare providers and health departments that use the bottles to “immediately begin to assess their situations and develop plans and options to mitigate the potential impact of the shortage on patient care.”
The advisory notes that the bottles are a key component in continuous-monitoring blood culture systems used to diagnose bloodstream infections and related conditions, such as endocarditis, sepsis, and catheter-related infections. About half of all US laboratories use the BD blood culture system, which is compatible only with the BACTEC bottles, the CDC advisory states.
Infectious disease specialist Krutika Kuppalli, MD (above), Chair of the Infectious Diseases Society of America (IDSA) and a Medical Officer for COVID-19 Health Operations at the World Health Organization, outlined the potential impact of the shortage on healthcare providers and clinical laboratories. “Without the ability to identify pathogens or [their susceptibility to specific antibiotics], patients may remain on broad antibiotics, increasing the risk of antibiotic resistance and Clostridium difficile-associated diarrhea,” she told STAT. “Shortages may also discourage ordering blood cultures, leading to missed infections that need treatment.” (Photo copyright: Loyola University Health System.)
FDA Advises Conservation of Existing BACTEC Supplies
The CDC advisory followed a July 10 notice from the US Food and Drug Administration (FDA) that also warned healthcare providers of “interruptions in the supply” of the bottles. The supply disruption “is expected to impact patient diagnosis, follow up patient management, and antimicrobial stewardship efforts,” the FDA’s letter states. “The FDA recommends laboratories and healthcare providers consider conservation strategies to prioritize the use of blood culture media bottles, preserving the supply for patients at highest risk.”
Hospitals have been warned that the bottle shortage could last until September, STAT reported.
BD issued a press release in which BD Worldwide Diagnostic Solutions President Nikos Pavlidis cast blame for the shortage on an unnamed supplier.
“We understand the critical role that blood culture testing plays in diagnosing and treating infections and are taking all available measures to address this important issue, including providing the supplier our manufacturing expertise, using air shipments, modifying BD manufacturing schedules for rapid production, and collaborating with the US Food and Drug Administration to review all potential options to mitigate delays in supply,” Pavlidis said. “As an additional stopgap measure, our former supplier of glass vials will restart production to help fill the intermittent gap in supply.”
Steps Clinical Laboratories Can Take
The CDC and FDA both suggested steps that clinical laboratories and other providers can take to conserve their supplies of the bottles.
Laboratories should strive to prevent contamination of blood cultures, which “can negatively affect patient care and may require the collection of more blood cultures to help determine whether contamination has occurred,” the CDC advised.
In addition, providers should “ensure that the appropriate volume is collected when collecting blood for culture,” the advisory states. “Underfilling bottles decreases the sensitivity to detect bacteremia/fungemia and may require additional blood cultures to be drawn to diagnose an infection.”
Laboratories should also explore alternative options, such as “sending samples out to a laboratory not affected by the shortage.”
The FDA advised providers to collect blood cultures “when medically necessary” in compliance with clinical guidelines, giving priority to patients exhibiting signs of a bloodstream infection.
In an email to STAT, Andrew T. Pavia, MD, Professor of Internal Medicine and Pediatrics at the University of Utah, offered examples of situations where blood culture tests are unnecessary according to clinical guidelines.
“There are conditions like uncomplicated community acquired pneumonia or skin infections where blood cultures are often obtained but add very little,” he told STAT. “It will be critical though that blood cultures are obtained from patients with sepsis, those likely to have bloodstream infections, and very vulnerable patients.”
Hospitals Already Addressing Shortage
STAT reported that some hospitals have already taken measures to reduce the number of tests they run. And some are looking into whether they can safely use bottles past their expiration dates.
Sarah Turbett, MD, Associate Director of Clinical Microbiology Laboratories at Massachusetts General Hospital in Boston, told STAT that her team tested bottles “that were about 100 days past their expiration date to see if they were still able to detect pathogens with the same efficacy as bottles that had not yet expired. They saw no difference in the time to bacterial growth—needed to detect the cause of an infection—in the expired bottles when compared to bottles that had not expired.”
Turbett pointed to a letter in the Journal of Clinical Microbiology and Infection in which European researchers found that bottles from a different brand “were stable for between four and seven months after their expiration dates,” STAT reported.
During a Zoom call hosted by the CDC and the IDSA, hospital representatives asked if the FDA would permit use of expired bottles. However, “a representative of the agency was not able to provide an immediate answer,” STAT reported.
With sepsis being the leading cause of death in hospitals, these specimen bottles for blood culture testing are essential in diagnosing patients with relevant symptoms. This is a new example of how the supply chain for clinical laboratory instruments, tests, and consumables—which was a problem during the SARS-CoV-2 pandemic—continues to be problematic in unexpected ways.
Taking a wider view of supply chain issues that can be disruptive to normal operations of clinical laboratories and anatomic pathology groups, the market concentration of in vitro diagnostics (IVD) manufacturers means fewer vendors offering the same types of products. Consequently, if a lab’s prime vendor has a supply chain issue, there are few options available to swiftly purchase comparable products.
A separate but related issue in the supply chain involves “just in time” (JIT) inventory management—made famous by Taiichi Ohno of Toyota back in the 1980s. This management approach was designed to deliver components and products to the user hourly, daily, and weekly, as appropriate. The goal was to eliminate the cost of carrying large amounts of inventory. This concept evolved into what today is called the “Lean Manufacturing” method.
However, as was demonstrated during the SARS-CoV-2 pandemic, manufacturers and medical laboratories that had adopted JIT found themselves with inadequate numbers of components and finished products.
In the case of the current shortage of BD blood culture media bottles, this is a real-world example of how market concentration limited the number of vendors offering comparable products. At the same time, if this particular manufacturer was operating with the JIT inventory management approach, it found itself with minimal inventories of these media bottles to ship to lab clients while it addressed the manufacturing problems that caused this shortage.
Researchers used CRISPR-based assays to develop new clinical laboratory point-of-care blood test which boasts accuracy, affordability, and accessibility
According to UPI, the test can “distinguish between influenza A and influenza B—the two main types of seasonal flu—as well as identifying more virulent strains like H1N1 and H3N2.”
Many research teams are working to develop paper-based diagnostic screening tests because of their lower cost to produce and usefulness in remote locations. Should this near-patient point-of-care test become clinically viable, it could mean shorter times to answer, enabling speedier diagnoses and earlier start of treatment.
It also means patient specimens do not have to be transported to a clinical laboratory for testing. And reduced cost per test makes it possible to test more people. This serves the public health aspect of monitoring outbreaks of influenza and other diseases and gives hope for improved treatment outcomes.
“Being able to tease apart what strain or subtype of influenza is infecting a patient has repercussions both for treating them and public health interventions, said Jon Arizti Sanz, PhD, co-lead study author and postdoctoral researcher at the Broad Institute of Harvard and MIT, in a Broad Institute news release.
“Ultimately, we hope these tests will be as simple as rapid antigen tests, and they’ll still have the specificity and performance of a nucleic acid test that would normally be done in a laboratory setting,” Cameron A. Myhrvold, PhD (above), Assistant Professor of Molecular Biology at Princeton University in New Jersey, told CIDRAP. Influenza tests that can be performed at the point of care and in remote locations may reduce the number of screening tests performed by clinical laboratories. (Photo copyright: Michael James Butts/Hertz Foundation.)
Her team developed their tests using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), “a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform,” the researchers wrote in their Journal of Molecular Diagnostics paper.
“SHINE has a runtime of 90 minutes, can be used at room temperature and only requires an inexpensive heat block to heat the reaction. The SHINE technology has previously been used to identify SARS-CoV-2 and later to distinguish between the Delta and Omicron variants,” Bioanalysis Zone reported.
“The test uses genetically engineered enzymes to identify specific sequences of viral RNA in samples,” the researchers told UPI. Originally designed to detect COVID-19, the team adapted the technology to detect influenza in 2022 “with the aim of creating a screening tool that could be used in the field or in clinics rather than hospitals or high-tech diagnostic labs,” they said.
Influenza A and B as well as H1N1 and H3N2 subtypes were the targets of the four SHINE assays. “When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously,” the researchers wrote in their paper.
The team used “20 nasal swabs from people with flu-like symptoms during the 2020-2021 flu season, nasal fluid from healthy people as the control, and 2016-2021 influenza sequences downloaded from the National Center for Biotechnology Information Influenza (NICB) database. They compared the results with those from quantitative reverse transcription-polymerase chain reaction (RT-PCR) tests,” CIDRAP reported.
The original 2020 test (shown above) takes 90 minutes to develop at room temperature. The test developers aim to drop this down to 15 minutes. In comparison, typical polymerase chain reaction (PCR) testing requires medical laboratories to have specialized equipment, trained staff, and prolonged processing times, the Broad Institute news release notes. (Photo copyright: Broad Institute.)
Implications of the New Tests
The ease of the new tests is an important development since approximately only 1% of individuals who come down with the flu see doctors for testing, according to the news release. And researchers had this in mind, looking at speed, accuracy, and affordability as a means to “improve outbreak response and infection care around the world,” UPI reported.
There are great benefits to strain differentiation that be achieved with the new test. Doctors are hopeful the test will help dial in the best treatment plans for patients since some strains are resistant to the antiviral medication oseltamivir (Tamiflu), UPI noted. This is significant since Tamiflu “is a common antiviral,” said Sanz in the Broad Institute news release.
“These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance,” the Journal of Molecular Diagnostics paper noted. This allows for more strategic treatment planning.
“Using a paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” said Ben Zhang, an MD candidate in the Health Sciences and Technology at Harvard and co-first author of the study, in the Broad Institute news release.
Future Plans for Tests
“With further development, the test strip could be reprogrammed to distinguish between SARS-CoV-2 and flu and recognize swine flu and avian flu, including the H5N1 subtype currently causing an outbreak in US dairy cattle,” the study authors told CIDRAP.
The team is also looking at ways to help prevent H5N1 from crossing into human contamination, Sanz told UPI.
The new Princeton/MIT/Harvard tests echo the trend to bring in affordability and ease-of-use with accurate results as an end goal. Faster results mean the best treatments for each person can start sooner and may render the transport of specimens to a clinical laboratory as a second step unnecessary.
As research teams work to develop paper-based viral tests for their plethora of benefits, clinical laboratories will want to pay close attention to this development as it can have a big implication on assisting with future outbreaks.
Additional research is needed before these tests are going to be commonplace in homes worldwide, but this first step brings inspiration and hope of what’s to come.
Study of the 50 Omicron variants could lead to new approaches to clinical laboratory testing and medical treatments for long COVID
Patients infected with SARS-CoV-2 can usually expect the COVID-19 illness to subside within a couple of weeks. However, one Dutch patient remained infected with the coronavirus for 612 days and fought more than 50 mutations (aka, variants) before dying late last year of complications due to pre-existing conditions. This extreme case has given doctors, virologists, microbiologists, and clinical laboratories new insights into how the SARS-CoV-2 virus mutates and may lead to new treatments for long COVID.
The medication the patient was taking for his pre-existing conditions may have contributed to his body being unable to produce antibodies in response to three shots of the Moderna mRNA COVID vaccine he received.
Magda Vergouwe, MD, PhD candidate at the Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, who lead a study into the patient, theorized that some of the medications the patient was on for his pre-existing conditions could have destroyed healthy cells alongside the abnormal cancer-causing B cells the drugs were meant to target.
“This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals,” the researchers said prior to presenting their report about the case at a meeting of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in Barcelona, Spain, Time reported. “We emphasize the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections.”
“Chronic infections and viral evolution [are] commonly described in [the] literature, and there are other cases of immunocompromised patients who have had [COVID] infections for hundreds of days,” Magda Vergouwe, MD, PhD candidate (above), Center for Experimental and Molecular Medicine at Amsterdam UMC, told Scientific American. “But this is unique due to the extreme length of the infection … and with the virus staying in his body for so long, it was possible for mutations to just develop and develop and develop.” Microbiologists, virologists, and clinical laboratories involved in testing patients with long COVID may want to follow this story. (Photo copyright: LinkedIn.)
Risks to Immunocompromised Patients
Pre-existing conditions increase the risk factor for COVID-19 infections. A 2021 study published in the Journal of the American Board of Family Medicine (JABFM) titled, “Prevalence of Pre-existing Conditions among Community Health Center Patients with COVID-19,” found that about 61% of that study’s test group had a pre-existing condition prior to the outbreak of the COVID-19 pandemic.
When the Dutch man was admitted to Amsterdam UMC with common and serious COVID-19 symptoms, such as shortness of breath, a cough, and low blood oxygen levels, he was prescribed sotrovimab (a monoclonal antibody) along with other COVID treatments.
About a month after being admitted his COVID-19 symptoms decreased, so he was first discharged to a rehab facility and then finally to his home. However, he continued to test positive for the coronavirus and developed other infections that may have been complicated by the persistent case of COVID-19.
The Amsterdam UMC doctors emphasized that the man ultimately succumbed to his pre-existing conditions and not necessarily COVID-19.
“It’s important to note that in the end he did not die from his COVID-19,” Vergouwe told Scientific American. “But he did keep it with him for a very long period of time until then, and this is why we made sure to sample [the virus in his body] as much as we could.”
One in Five Adults Develop Long COVID
Long COVID does not necessarily indicate an active infection. However, in as many as one in five US adults COVID symptoms persist after the acute phase of the infection is over, according to a study published recently in JAMA Network Open titled, “Epidemiologic Features of Recovery from SARS-CoV-2 Infection.”
“In this cohort study, more than one in five adults did not recover within three months of SARS-CoV-2 infection. Recovery within three months was less likely in women and those with pre-existing cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave,” the JAMA authors wrote.
The origins of long COVID are not entirely clear, but according to the National Institutes of Health (NIH) it can develop when a patient is unable to sufficiently rest while battling off the initial virus. According to Vergouwe, the SARS-CoV-2 genome will always grow quicker when found in a patient with a compromised immune system.
Unique COVID-19 Mutations
More than 50 new mutations of the original Omicron variant were identified in the Dutch patient. According to Vergouwe, “while that number can sound shocking, mutations to the SARS-CoV-2 genome are expected to evolve more quickly in those who are immunocompromised (the average mutation rate of the virus is estimated to be two mutations per person per month),” Scientific American reported. “What does make these mutations unusual, she noted, is how their features differed vastly from mutations observed in other people with COVID. [Vergouwe] hypothesizes that the exceptional length of the individual’s infection, and his pre-existing conditions, allowed the virus to evolve extensively and uniquely.”
COVID-19 appears to be here to stay, and most clinical laboratory managers and pathologists understand why. As physicians continue to learn about the SARS-CoV-2 coronavirus, this is another example of how the knowledge about SARS-CoV-2 is growing as different individuals are infected with different variants of the virus.
