New studies show that children and teens are developing long COVID at higher rates—especially after multiple infections. Here’s how clinical labs can play a vital role in identifying at-risk patients and supporting early intervention.
As the healthcare system continues to grapple with the lingering effects of COVID-19, new research is drawing attention to a growing—and often overlooked—population: children and teens with long COVID. For clinical laboratory leaders, these findings underscore the continued importance of SARS-CoV-2 testing, variant monitoring, and post-infection diagnostics in younger patients. Studies reviewed by the Center for Infectious Disease Research and Policy (CIDRAP) and others show that long COVID is not only prevalent in youth but more likely to develop after reinfection. With an estimated one million U.S. children already affected, labs play a critical role in helping clinicians identify and manage post-viral complications while providing data that inform vaccine and reinfection risk strategies.
The pooled results of the studies found that long COVID prevalence was 36% among patients who had become infected with the SARS-CoV-2 infection. The highest prevalence was found in South America, and risk factors included being unvaccinated for the virus, contracting a pre-Omicron variant, and being of the female sex.
Another study analyzed from The Journal of Infectious Diseases focused on the effects of long COVID on adolescents in the summer of 2022. In that study, at least one symptom lasted for four weeks or more for 41% of the respondents who also tested positive for a SARS-CoV-2 infection. Adolescents in the study who tested positive also had increased odds of developing neurological symptoms that lasted three months or longer compared to the adolescents in the study who tested negative for SARS-CoV-2. However, the study also concluded that most symptoms are resolved within three months of infection.
Risk Increases with Multiple Infections
The New York Timesrecently reported that a study published in Lancet Infectious Diseases found that children and teenagers are twice as likely to develop long COVID if they became infected with the virus more than once. The study was a part of the National Institutes of Health’s RECOVER Initiative by examining the records of around 465,000 young people under 21 at 40 United States children’s hospitals.
Over a six-month period, it was found that 1,884 per million young people would develop long COVID after being infected with the virus twice, whereas only 904 per million young people developed long COVID after one infection. The exact numbers of young people with long COVID is not known. However, the Centers for Disease Control and Prevention (CDC) estimates the number stands at about 1 million American children, or 1.3% of the population under 18. A similar trend is seen in adults with long COVID.
These numbers are likely conservative, and the issue of long COVID among youth may be more widespread. According to the same study, tens of thousands of young people in the study were treated for conditions associated with long COVID, such as respiratory symptoms and abdominal pain. Yong Chen, PhD, senior author of the study and professor of Biostatistics at Department of Biostatistics, Epidemiology, and Informatics (DBEI), and a Senior Scholar at Center for Clinical Epidemiology & Biostatistics (CCEB) at the University of Pennsylvania (Penn) Perelman School of Medicine, noted the limitations of the diagnostic code. As quoted by The New York Times, he called the findings a mere “subset of the long COVID.”
Yong Chen, PhD, professor of Biostatistics at DBEI, and a Senior Scholar at CCEB at the University of Pennsylvania (Penn) Perelman School of Medicine said, “Your body really has a memory system and is really going to be hurt from recurrent infection.” (Photo credit: University of Pennsylvania)
Mitigating Risk
Now that we are over five years past the initial worldwide lockdowns, the public has begun to live with significantly less fear–– but the risk remains. “People think that reinfections don’t matter as much and don’t take them seriously,” Chen told Time, “Our primary message is that reinfections still matter, and you should do what you can to avoid reinfection by taking a vaccine or wearing a mask.”
However, the CDC has recently approved recommendations made by Health and Human Services Secretary, Robert F. Kennedy Jr., to remove the blanket recommendation for adults 65 and older to be vaccinated against COVID-19 and recommended that patients between six months and 64 years should discuss with their doctors. Critics of the move warn that these ‘softer’ recommendations may limit insurance coverage of the vaccines.
Clinical laboratory professionals should remain vigilant as research continues to reveal how long COVID affects younger populations. The persistence and variability of post-COVID symptoms highlight the need for continued diagnostic vigilance and testing innovation—not only to confirm infection but to monitor lingering inflammatory, respiratory, or neurological effects. By maintaining awareness of evolving studies and updated guidance from public health agencies, labs can help clinicians identify which patients may be at higher risk for long-term complications. Moreover, laboratory data can support broader efforts to track reinfection patterns, inform vaccine strategies, and guide local health systems in managing the ongoing burden of COVID-related chronic illness.
Lead author of a new study, Ciro Chiappini, PhD, says this new technology could lead to advancements in personalized medicine
Scientists at King’s College London have developed a nanoneedle patch that offers a painless alternative to biopsies that also delivers quicker and more accurate results.
As reported by Phys Org, new research published in Nature Nanotechnology shows that these new patches could be the future of diagnostics. As common as traditional biopsies are, they can be painful and often patients are deterred from follow-ups as well as seeking out treatment and early diagnosis.
“We have been working on nanoneedles for twelve years, but this is our most exciting development yet. It opens a world of possibilities for people with brain cancer, Alzheimer’s, and for advancing personalized medicine. It will allow scientists—and eventually clinicians—to study disease in real time like never before.” said Ciro Chiappini, PhD, senior lecturer at King’s College London and lead author of the study.
The lead author of the study, Ciro Chiappini, PhD, senior lecturer at King’s College London said the new development doesn’t disrupt the cell membrane in a way that cannot be repaired. (Photo copyright: King’s College London)
How it Works
The patches are made up of tens of millions of microscopic needles that are 1,000 times thinner than a human hair and do not remove tissue. This causes no damage and pain while the nanoneedles extract molecular fingerprints from the tissue. The sample is then analyzed using both mass spectrometry and artificial intelligence.
“This approach provides multidimensional molecular information from different types of cells within the same tissue. Traditional biopsies simply cannot do that. And because the process does not destroy the tissue, we can sample the same tissue multiple times, which was previously impossible.” said Chiappini of the process. The study focused on lipids and applied the patch to brain cancer tissue of human origin and mice.
Potential Limitations
Additional reporting by Science News looks into some of the possible drawbacks of the technology.
The patch can’t sample tissue that exists deeper in the body, yet Chiappini says that physicians can use the patch during surgery to get fast results on tissue they are operating on. “It’s very much a surface technology, which is potentially [both] a limitation and a feature,” he says.
Phys Org explained the potential during brain surgery. A surgeon would apply a patch to a “suspicious area” and receive results within 20 minutes, providing the surgical team with impactful information in real-time.
Less Pain, More Gain?
It is no secret that patients will often try to avoid or put off uncomfortable medical procedures like biopsies. This new development is part of an ongoing larger trend—making medical procedures more appealing to encourage higher percentages of patients to seek care and receive treatment. As recently reported by Dark Daily in the article entitled, “University of Texas Study Shows Self-Collection Boosts Cancer Screenings among Women,” a new at-home collection kit to replace a traditional Pap smear may help boost early detection of cervical cancer in women.
This new technology and trend toward less painful procedures suggests that patients will be more inclined to participate in pathology exams if they were less invasive and uncomfortable or painful. Pathology professionals should keep on eye on future developments in this space.
Biopsies are not yet ready to become obsolete, as the patch is still in its early stages and more research is needed.
The St. Louis-based in vitro diagnostics (IVD) developer is making PrecivityAD available to physicians while awaiting FDA clearance for the non-invasive test
Clinical laboratories have long awaited a test for Alzheimer’s disease and the wait may soon be over. The first blood test to aid physicians and clinical laboratories in the diagnosis of patients with memory and cognitive issues has been released by C₂N Diagnostics of St. Louis. The test measures biomarkers associated with amyloid plaques in the brain—the pathological hallmark of Alzheimer’s.
In a news release, PrecivityAD describes the laboratory-developed test (LDT) as “a highly sensitive blood test using mass spectrometry and is performed in C₂N’s CLIA-certified laboratory. While the test by itself cannot diagnose Alzheimer’s disease … the test is an important new tool for physicians to aid in the evaluation process.”
PrecivityAD provides physicians with an Amyloid Probability Score (APS) for each patient. For example:
A low APS (0-36) is consistent with a negative amyloid PET scan result and, thus, has a low likelihood of amyloid plaques, an indication other causes of cognitive symptoms should be investigated.
An intermediate APS (37-57) does not distinguish between the presence or absence of amyloid plaques and indicates further diagnostic evaluation may be needed to assess the underlying cause(s) for the patient’s cognitive symptoms.
A high APS (58-100) is consistent with a positive amyloid positron-emission tomography (PET) scan result and, thus, a high likelihood of amyloid plaques. Presence of amyloid plaques is consistent with an Alzheimer’s disease diagnosis in someone who has cognitive decline, but alone is insufficient for a final diagnosis.
The $1,250 test is not currently covered by health insurance or Medicare. However, C₂N Diagnostics has pledged to offer discounts to patients based on income levels.
Jeff Cummings, MD, ScD (above) Research Professor, Department of Brain Health, University of Nevada, Las Vegas, said in a C₂N Diagnostics press release, “A blood test for Alzheimer’s is a game changer.” While there is no cure for Alzheimer’s, a non-invasive blood test can help providers diagnose patients when their symptoms are mild and often misdiagnosed. “Advances in Alzheimer’s diagnostics are key to more effective identification, diagnosis, and clinical trial recruitment,” he added. Currently, brain changes caused by the disease are most commonly identified through PET scans. (Photo copyright: University of Nevada Las Vegas.)
Additional Research Requested
While C₂N’s PrecivityAD is the first test of its kind to reach the commercial market, it has not received US Food and Drug Administration (FDA) clearance, nor has the company published detailed data on the test’s accuracy. However, the PrecivityAD website says the laboratory-developed test “correctly identified brain amyloid plaque status (as determined by quantitative PET scans) in 86%” of 686 patients, all of whom were older than 60 years of age with subjective cognitive impairment or dementia.
But some Alzheimer’s advocacy groups are tempering their enthusiasm about the breakthrough. Eliezer Masliah, MD, Director of the Division of Neuroscience, National Institute on Aging, told the Associated Press (AP), “I would be cautious about interpreting any of these things,” he said of the company’s claims. “We’re encouraged, we’re interested, we’re funding this work, but we want to see results.”
Heather Snyder, PhD, Vice President, Medical and Scientific Relations at the Alzheimer’s Association told the AP her organization will not endorse a test without FDA clearance. The Alzheimer’s Association also would like to see the test studied in larger and diverse populations. “It’s not quite clear how accurate or generalizable the results are,” she said.
Braunstein defended the decision to make the test for Alzheimer’s immediately available to physicians, asking in the AP article, “Should we be holding that technology back when it could have a big impact on patient care?”
Howard Fillit, MD, Founding Executive Director and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF), maintains the first-of-its-kind blood test is an important milestone in Alzheimer’s research. ADDF invested in C₂N’s development of the test.
“Investing in biomarker research has been a core goal for the ADDF because having reliable, accessible, and affordable biomarkers for Alzheimer’s diagnosis is step one in finding drugs to prevent, slow, and even cure the disease,” Fillit said in an ADDF news release.
C₂N is also developing a Brain Health Panel to detect multiple blood-based markers for Alzheimer’s disease that will aid in better disease staging, treatment monitoring, and differential diagnosis.
Second Alzheimer’s Test in Development
Soon medical laboratories may have two different in vitro diagnostic tests for Alzheimer’s disease. On December 2, Fujirebio Diagnostics filed for FDA 510(k) premarket clearance for its Lumipulse G β-Amyloid Ratio (1-42/1-40) test, which looks for biomarkers found in cerebral spinal fluid.
“Accurate and earlier intervention will also facilitate the development of new drug therapies, which are urgently needed as the prevalence of Alzheimer’s disease increases with a rapidly aging population globally,” Fujirebio Diagnostics President and CEO Monte Wiltse said in a news release.
The Lumipulse G β-Amyloid test, which is intended for use in patients aged 50 and over presenting with cognitive impairment, has received CE-marking for use in the European Union.
Clinical laboratory managers will want to keep a close eye on rapidly evolving developments in testing for Alzheimer’s disease. It is the sixth leading cause of death in the United States and any clinical laboratory test that could produce an early and accurate diagnosis of Alzheimer’s Disease would become a valuable tool for physicians who treat patients with the symptoms of Alzheimer’s.
The AI protein-structure-prediction system may ‘revolutionize life sciences by enabling researchers to better understand disease,’ researchers say
Genomics leaders watched with enthusiasm as artificial intelligence (AI) accelerated discoveries that led to new clinical laboratory diagnostic tests and advanced the evolution of personalized medicine. Now Google’s London-based DeepMind has taken that a quantum step further by demonstrating its AI can predict the shape of proteins to within the width of one atom and model three-dimensional (3D) structures of proteins that scientist have been trying to map accurately for 50 years.
Pathologists and clinical laboratory professionals know that it is estimated that there are around 30,000 human genes. But the human proteome has a much larger number of unique proteins. The total number is still uncertain because scientists continue to identify new human proteins. For this reason, more knowledge of the human protein is expected to trigger an expanding number of new assays that can be used by medical laboratories for diagnostic, therapeutic, and patient-monitoring purposes.
DeepMind’s AI tool is called AlphaFold and the protein-structure-prediction system will enable scientists to quickly move from knowing a protein’s DNA sequence to determining its 3D shape without time-consuming experimentation. It “is expected to accelerate research into a host of illnesses, including COVID-19,” BBC News reported.
This protein-folding breakthrough not only answers one of biology’s biggest mysteries, but also has the potential to revolutionize life sciences by enabling researchers to better understand disease processes and design personalized therapies that target specific proteins.
In November, DeepMind’s AlphaFold won the 14th Community Wide Experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP14), a biennial competition in which entrants receive amino acid sequences for about 100 proteins whose 3D structures are unknown. By comparing the computational predictions with the lab results, each CASP14 competitor received a global distance test (GDT) score. Scores above 90 out of 100 are considered equal to experimental methods. AlphaFold produced models for about two-thirds of the CASP14 target proteins with GDT scores above 90, a CASP14 press release states.
According to MIT Technology Review, DeepMind’s discovery is significant. That’s because its speed at predicting the structure of proteins is unprecedented and it matched the accuracy of several techniques used in clinical laboratories, including:
Unlike the laboratory techniques, which, MIT noted, are “expensive and slow” and “can take hundreds of thousands of dollars and years of trial and error for each protein,” AlphaFold can predict a protein’s shape in a few days.
“AlphaFold is a once in a generation advance, predicting protein structures with incredible speed and precision,” Arthur D. Levinson, PhD, Founder and CEO of Calico Life Sciences, said in a DeepMind blogpost. “This leap forward demonstrates how computational methods are poised to transform research in biology and hold much promise for accelerating the drug discovery process.”
Science reported that AlphaFold, which scored a median of 87—25 points above the next best predictions—did so well that CASP14 organizers worried DeepMind may have been somehow cheated. To validate the results, they asked AlphaFold to complete a “special challenge”—modeling a membrane protein from an ancient species of microbes called archaea, which they had been unable to model satisfactorily using X-ray crystallography. AlphaFold returned a detailed image of a three-part protein with two long helical arms in the middle. “It’s almost perfect,” Andrei Lupas, PhD, Director at the Max Planck Institute for Developmental Biology, told Science. “They could not possibly have cheated on this. I don’t know how they do it.” (Graphic copyright: DeepMind/Nature.)
“Even tiny rearrangements of these vital molecules can have catastrophic effects on our health, so one of the most efficient ways to understand disease and find new treatments is to study the proteins involved,” Moult said in the CASP14 press release. “There are tens of thousands of human proteins and many billions in other species, including bacteria and viruses, but working out the shape of just one requires expensive equipment and can take years.”
Science reported that the 3D structures of only 170,000 proteins have been solved, leaving roughly 200 million proteins that have yet to be modeled. Therefore, AlphaFold will help researchers in the fields of genomics, microbiomics, proteomics, and other omics understand the structure of protein complexes.
“Being able to investigate the shape of proteins quickly and accurately has the potential to revolutionize life sciences,” Andriy Kryshtafovych, PhD, Project Scientist at University of California, Davis, Genome Center, said in the press release. “Now that the problem has been largely solved for single proteins, the way is open for development of new methods for determining the shape of protein complexes—collections of proteins that work together to form much of the machinery of life, and for other applications.”
Clinical laboratories play a major role in the study of human biology. This breakthrough in genomics research and new insights into proteomics may provide opportunities for medical labs to develop new diagnostic tools and assays that better identify proteins of interest for diagnostic and therapeutic purposes.
Washington Post investigation outlines scientists’ frustrations in the early days of the pandemic, as they worked to deploy laboratory-developed tests for the novel coronavirus
In the wake of the failed rollout of the Centers for Disease Control and Prevention’s (CDC) COVID-19 diagnostic test last February, many CLIA-certified academic and public health laboratories were ready, and had the necessary resources, to develop their own coronavirus molecular diagnostic tests to help meet the nationwide demand for clinical laboratory testing. However, the response from the US Food and Drug Administration (FDA) was, in essence, “not so fast.”
In this second part of Dark Daily’s two-part e-briefing, we continue our coverage of the Washington Post (WP) investigation that detailed the regulatory hurdles which blocked private laboratories from deploying their own laboratory-developed tests (LDTs) for COVID-19. The report is based on previously unreported email messages and other documents reviewed by the WP, as well as the newspaper’s exclusive interviews with scientists and officials involved.
The CDC’s COVID-19 test kits began arriving at public health laboratories on February 8, just 18 days after the first case of the novel coronavirus was confirmed in the US. As the WP noted in an earlier analysis, titled, “What Went Wrong with Coronavirus Testing in the US,” the CDC’s decision to develop its own test was not surprising. “The CDC will develop [its] own test that is suited to an American healthcare context and the regulations that exist here,” explained Jeremy Konyndyk, Senior Policy Fellow at the Center for Global Development. “That’s how we normally would do things.”
But state and local public health laboratories quickly discovered that the CDC test kits were flawed due to problems with one of the reagents. While numerous academic, research, and commercial labs had the capability to produce their own COVID-19 PCR tests, FDA rules initially prevented them from doing so without a federal Emergency Use Authorization (EUA).
The bureaucratic hurdles arose due to Health and Human Services Secretary Alex Azar’s January 31 declaration that COVID-19 was a “health emergency” in the US. By doing so, HHS triggered a mandate that requires CLIA-certified labs at universities, research centers, and hospitals to seek an EUA from the FDA before deploying any laboratory-developed tests.
Scientists, Clinical Laboratories Frustrated by Bureaucratic Delays and Red Tape
To make matters worse, the EUA process was neither simple nor fast, which exasperated lab scientists and clinical laboratory administrators. “In their private communications, scientists at academic, hospital, and public health labs—one layer removed from federal agency operations—expressed dismay at the failure to move more quickly, and frustration at bureaucratic demands that delayed their attempts to develop alternatives to the CDC test,” wrote the WP investigators.
In a Feb. 27 email to other microbiologists, Marc Couturier, PhD, Medical Director at ARUP Laboratories, a national reference laboratory network located in Utah, voiced his irritation with the red tape that stymied private laboratory development of COVID-19 tests. He wrote, “We have the skills and resources as a community, but we are collectively paralyzed by a bloated bureaucratic/administrative process,” reported the WP.
Keith Jerome, MD, PhD (above), Head of the Virology Division at the Fred Hutchinson Cancer Research Center in Seattle, maintains federal regulations muted one of the nation’s greatest assets in the fight against COVID-19. “The great strength the US has always had, not just in virology, is that we’ve always had a wide variety of people and groups working on any given problem,” he told MIT Technology Review. “When we decided all coronavirus testing had to be done by a single entity, even one as outstanding as CDC, we basically gave away our greatest strength.” (Photo copyright: Jonathan Hamilton/NPR.)
‘FDA Should Not Treat Labs Like They Are Creating Commercial Products’
According to Kaiser Health News (KHN), Greninger was able to identify one of the nation’s first cases of community-acquired COVID-19 by taking “advantage of a regulatory loophole that allowed the lab to test samples obtained for research purposes from UW’s hospitals.”
But navigating the EUA process was a different story, Greninger told the WP. He spent more than 100 hours filling out forms and collecting information needed for the EUA application. After emailing the application to the FDA, Greninger received a reply containing eCopy Guidance telling him he needed to resubmit the information to the Document Control Center (DCC) at the Center for Devices and Radiological Health (CDRH), a federal agency Greninger knew nothing about. Another FDA rule required that the submission be copied to a hard disk and mailed to the DCC.
In an interview with ProPublica, Greninger stated that after he submitted his COVID-19 test—which copies the CDC protocol—an FDA reviewer told him he would need to prove the test would not show a positive result for someone infected with either a SARS or MERS coronavirus. The first SARS coronavirus disappeared in mid-2003 and the only two cases of MERS in the US were diagnosed in 2014. Greninger told ProPublica it took him two days to locate a clinical laboratory that could provide the materials he needed.
Greninger maintains the FDA should not treat all clinical laboratories as though they are making a commercial product. “I think it makes sense to have this regulation when you’re going to sell 100,000 widgets across the US. That’s not who we are,” he told ProPublica.
FDA Changes Course
Under pressure from clinical laboratory scientists and medical doctors, by the end of February the FDA had issued new policy that enabled CLIA-certified laboratories to immediately use their validated COVID-19 diagnostics while awaiting an EUA. “This policy change was an unprecedented action to expand access to testing,” said the FDA in a statement.
Since then, the FDA has continued to respond—albeit slowly—to scientists’ complaints about regulations that hampered the nation’s COVID-19 testing capacity.
Clinical laboratory leaders and pathologists involved in testing for the SARS-CoV-2 coronavirus should monitor the FDA’s actions and be aware of when and if certain temporary changes the agency implemented during the early days of the COVID-19 pandemic become permanent.
To read part one of our two-part coverage of the Washington Post’s investigation, click here.
