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Clinical Laboratories and Pathology Groups

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American Cancer Society Annual Report Shows Cervical Cancer Rate Increasing, but Only among 30- to 40-Year-Olds

Lack of regular clinical laboratory screenings in this age group at least partially to blame, researchers say

While cervical cancer rates have seen a 50-year decline overall, that trend is shifting among 30- to 40 year-olds who have experienced a near 2% increase from 2012-2019. This finding comes from a 2024 American Cancer Society (ACS) report that is eyeing the timeline of the human papillomavirus (HPV) vaccines and the lack of clinical laboratory cancer screenings as possible contributors to this new trend.

Though a 2% increase is significant, the study, which was published in CA: A Cancer Journal for Clinicians, titled “Cancer Statistics, 2024,” noted that these cancers were “mostly early, curable tumors,” epidemiologist Ahmedin Jemal DVM, PhD, Senior Vice President Surveillance and Health Equity Science at ACS, and senior author of the new report, told NBC News.

To understand how the increase in cancer rates impacts this age group, consider the numbers: “About 13,800 American women are diagnosed with cervical cancer each year and 4,360 die from the disease,” NBC reported.

US vaccination programs for youths have lagged behind nations that have embraced HPV vaccination to positive results.

Australia, for example, has vaccinated a high proportion of its youth since the vaccine was first released in 2006. In 2023, the nation created its National Strategy for the Elimination of Cervical Cancer in Australia program and expects cervical cancer to be fully eliminated there by 2035.

For lab professionals, this demonstrates how new technologies like the HPV test and vaccine can alter how individuals are screened for diseases, and how vaccines can reduce and even eliminate diseases that were once common.

“We need to make sure we are not forgetting about that generation that was a little too old for HPV vaccination,” Jennifer Spencer, PhD (above), Assistant Professor, Department of Population Health and Department Internal Medicine, Dell Medical School, University of Texas at Austin, told NBC News. “The onus is on the healthcare system to think about who is slipping through the cracks,” she added. Lack of clinical laboratory screenings among the 30-40 age group may be contributing to the increase in cervical cancer rates. (Photo copyright: Dell Medical School.)

Lack of Clinical Laboratory Screenings

Research points to a lag in cervical cancer screenings as a possible cause for the recent rise in cases. Timely screening allows doctors to both identify and remove any worrisome lesions before they become cancerous, Jennifer Spencer, PhD, Assistant Professor of the Department of Population Health, Dell Medical School, University of Texas at Austin, told NBC News.

Spencer was not involved in the American Cancer Society study, but rather had her own study published in the American Journal of Preventative Medicine in 2023 titled, “Racial and Ethnic Disparities in Cervical Cancer Screening from Three US Healthcare Settings.”

Screenings for women ages 21-65 have fallen 15% since 2000, according to data from the National Cancer Institute. Also, more than half of women with cervical cancer have “either never been screened or haven’t been screened in the past five years, according to the Centers for Disease Control and Prevention,” NBC reported.

The US Preventative Services Task Force recommends that women 21-29 years of age should receive Pap smears every three years. Women 30-65 years of age should do the same, or every five years with an HPV test or combo test.

Despite a decrease in cervical cancer, 29% of women in their 20s are overdue to get screening, NBC noted. This was the age group most likely to be lagging on getting screened. Spencer says that this delay in screening could explain the resulting increase in cervical cancer among the 30-40 age group.

Causes for Lack in Screenings

Regardless of age group, women who were uninsured, in a rural area, non-white, or identifying as lesbian, bisexual, or gay were also more likely to be overdue on screenings, according to Spencer’s study.

In addition, women who just moved to the United States may have missed their screenings, thus increasing risk, epidemiologist Nicholas Wentzensen, MD, PhD, Deputy Director, Senior Investigator, and Head of the Clinical Epidemiology Unit at the National Cancer Institute, told NBC News.

Additionally, Spencer found in her research that confusion exists by both patients and doctors on when cervical screening should take place. Some participants in her study did not have screening recommended by their doctors, while others simply did not recognize it was necessary.

“When women in one of Spencer’s studies were asked why they hadn’t been screened recently, they commonly said that they didn’t know they needed to be screened or that a health provider hadn’t recommended it. Only 1% [of] women ages 21 to 29 said they had skipped screening because they had received the HPV shot,” NBC News reported.

A 2022 Journal of American Medicine (JAMA) report also looked at screenings as a possible cause. Those researchers found that “only 73% of women with abnormal screening results received follow-up care,” NBC reported.

“If the increase (in cases) is real, it could be a result of missed screening opportunities at earlier ages, as suggested by the increase in squamous cell carcinoma and localized disease. It may also stem from a decrease in screening at younger ages,” the JAMA study authors wrote.

HPV Vaccine and Cervical Cancer Prevention

The HPV vaccine is another important area of research to be considered. Approved in 2006, HPV vaccines were beneficial because HPV “causes six types of cancer, including cervical cancer,” NBC reported.

Women in their early 20s at that time were the first generation to benefit from HPV vaccines, NBC noted. It may be that they continue to benefit in a decrease in cervical cancer among their cohort.

Countries that have emphasized HPV vaccines and stringent screenings in their cancer prevention efforts are reaping the benefits of that policy.

In “Australia Moves to Fully Eliminate Cervical Cancer by 2035, Especially in Underserved and Diverse Populations,” Dark Daily reported how Australia was one of the first nations to implement HPV vaccination programs. By 2010, Australia was working to vaccinate every child. Now, 14 years later, the pool of adults vaccinated against HPV in that nation is causing the rates of cervical cancer to fall.

Follow-through is Key for Patients

Though cancer screening and the HPV vaccine are important first steps women should take to prevent cervical cancer, follow-through clinical laboratory testing and diagnosis is crucial, Spencer added. This would include additional testing and treatment for any abnormal results of the cancer screening.

However, according to Spencer, “only 73% of women with abnormal screening results received follow-up care,” NBC reported.

Healthcare policymakers today are emphasizing the need for providers to identify and close gaps in care as a way to improve patient outcomes and help control the cost of care. Women who are overdue for a cervical cancer screening test—whether an HPV test or Pap smear—have this care gap. This creates an opportunity for clinical labs to add value.

Clinical laboratories could be helpful during this period by looking at patient files to note which patients are overdue for screenings and then alerting their doctors. Medical labs also could work directly with doctors to establish a program to reach out to patients. Labs would thus be adding value as well as benefitting patients.

—Kristin Althea O’Connor

Related Information:

Cervical Cancer Increasing in Women in Their 30s and 40s, New Report Finds

Cervical Cancer Incidence among US Women, 2001-2019

Cancer Statistics, 2024

Racial and Ethnic Disparities in Cervical Cancer Screening from Three US Healthcare Settings

Australia Moves to Fully Eliminate Cervical Cancer by 2035, Especially in Underserved and Diverse Populations

Wiley Launches Paper Mill Detection Tool after Losing Millions Due to Fraudulent Journal Submissions

Groups representing academic publishers are taking steps to combat paper mills that write the papers and then sell authorship spots

Clinical laboratory professionals rely on peer-reviewed research to keep up with the latest findings in pathology, laboratory medicine, and other medical fields. They should thus be interested in new efforts to combat the presence of “research paper mills,” defined as “profit oriented, unofficial, and potentially illegal organizations that produce and sell fraudulent manuscripts that seem to resemble genuine research,” according to the Committee on Publication Ethics (COPE), a non-profit organization representing stakeholders in academic publishing.

“They may also handle the administration of submitting the article to journals for review and sell authorship to researchers once the article is accepted for publication,” the COPE website states.

In a recent example of how paper mills impact scholarly research, multinational publishing company John Wiley and Sons (Wiley) announced in The Scholarly Kitchen last year that it had retracted more than 1,700 papers published in journals from the company’s Hindawi subsidiary, which specializes in open-access academic publishing.

“Often journals will invite contributions to a special issue on a specific topic and this provides an opening for paper mills to submit often many publications to the same issue,” explained a June 2022 research report from the COPE and the International Association of Scientific Technical and Medical Publishers (STM).

“In Hindawi’s case, this is a direct result of sophisticated paper mill activity,” wrote Jay Flynn, Wiley’s Executive Vice President and General Manager, Research, in a Scholarly Kitchen guest post. “The extent to which our processes and systems were breached required an end-to-end review of every step in the peer review and publishing process.”

In addition, journal indexer Clarivate removed 19 Hindawi journals from its Web of Science list in March 2023, due to problems with their editorial quality, Retraction Watch reported.

Hindawi later shut down four of the journals, which had been “heavily compromised by paper mills,” according to a blog post from the publisher.

Wiley also announced at that time that it would temporarily pause Hindawi’s special issues publishing program due to compromised articles, according to a press release.

“We urgently need a collaborative, forward-looking and thoughtful approach to journal security to stop bad actors from further abusing the industry’s systems, journals, and the communities we serve,” wrote Jay Flynn (above), Wiley EVP and General Manager, Research and Learning, in an article he penned for The Scholarly Kitchen. “We’re committed to addressing the challenge presented by paper mills and academic fraud head on, and we invite our publishing peers, and the many organizations that work alongside us, to join us in this endeavor.” Clinical laboratory leaders understand the critical need for accurate medical research papers. (Photo copyright: The Scholarly Kitchen.)

Using AI to Detect Paper Mill Submissions

Wiley acquired Hindawi in 2021 in a deal valued at $298 million, according to a press release, but the subsidiary has since become a financial drain for the company.

The journals earn their revenue by charging fees to authors. But in fiscal year 2024, which began last fall, “Wiley expects $35-40 million in lost revenue from Hindawi as it works to turn around journals with issues and retract articles,” Retraction Watch reported, citing an earnings call.

Wiley also revealed that it would stop using the Hindawi brand name and bring the subsidiary’s remaining journals under its own umbrella by the middle of 2024.

To combat the problem, Wiley announced it would launch an artificial intelligence (AI)-based service called Papermill Detection in partnership with Sage Publishing and the Institute of Electrical and Electronics Engineers (IEEE).

The service will incorporate tools to detect signs that submissions originated from paper mills, including similarities with “known papermill hallmarks” and use of “tortured phrases” indicating that passages were translated by AI-based language models, according to a press release.

These tools include:

  • Papermill Similarity Detection: Checks for known papermill hallmarks and compares content against existing papermills papers.
  • Problematic Phrase Recognition: Flags unusual alternatives to established terms.
  • Unusual Publication Behavior Detection: Identifies irregular publishing patterns by paper authors.
  • Researcher Identity Verification: Helps detect potential bad actors.
  • Gen-AI Generated Content Detection: Identifies potential misuse of generative AI.
  • Journal Scope Checker: Analyzes the article’s relevance to the journal.

The company said that the new service will be available through Research Exchange, Wiley’s manuscript submission platform, as early as next year.

Other Efforts to Spot Paper Mill Submissions

Previously, STM announced the launch of the STM Integrity Hub, with a mission “to equip the scholarly communication community with data, intelligence, and technology to protect research integrity,” Program Director Joris van Rossum, PhD, told The Scholarly Kitchen.

In 2023, the group announced that the hub would integrate Papermill Alarm from Clear Skies, a paper mill detection tool launched in 2022 with a focus on cancer research. It uses a “traffic-light rating system for research papers,” according to a press release.

In an announcement about the launch of Wiley’s Papermill Detection service, Retraction Watch suggested that one key to addressing the problem would be to reduce incentives for authors to use paper mills. Those incentives boil down to the pressure placed on many scientists, clinicians, and students to publish manuscripts, according to the research report from STM and COPE.

In one common scenario, the report noted, a paper mill will submit a staff-written paper to multiple journals. If the paper is accepted, the company will list it on a website and offer authorship spaces for sale.

“If a published paper is challenged, the ‘author’ may sometimes back down and ask for the paper to be retracted because of data problems, or they may try to provide additional supporting information including a supporting letter from their institution which is also a fake,” the report noted.

All of this serves as a warning to pathologists and clinical laboratory professionals to carefully evaluate the sources of medical journals publishing studies that feature results on areas of healthcare and lab medicine research that are of interest.

—Stephen Beale

Related Information:

Potential “Paper Mills” and What to Do about Them: A Publisher’s Perspective

Up to One in Seven Submissions to Hundreds of Wiley Journals Flagged by New Paper Mill Tool

Guest Post: Addressing Paper Mills and a Way Forward for Journal Security

Paper Mills Research Report from COPE and STM

Wiley Paused Hindawi Special Issues amid Quality Problems, Lost $9 Million in Revenue

‘The Situation Has Become Appalling’: Fake Scientific Papers Push Research Credibility to Crisis Point

Publisher Retracts More than a Dozen Papers at Once for Likely Paper Mill Activity

STM Integrity Hub Incorporates Clear Skies’ Papermill Alarm Screening Tool

The New STM Integrity Hub

Upholding Research Integrity in the Age of AI

From Regulations to Innovations: Annual Executive War College Convenes in New Orleans

29th Conference Features Information on What Clinical Lab Leaders Need to Know About a ‘Perfect Storm’ of New Compliance Challenges

There are signs that the US Food and Drug Administration (FDA) is poised to release the final rule on laboratory developed tests (LDTs)—perhaps even during the 29th annual Executive War College on Diagnostic, Clinical Laboratory, and Pathology Management, which kicks off in New Orleans this week.

The Office of Management and Budget (OMB) concluded its review of the final rule on April 22. Former FDA commissioner Scott Gottlieb, MD, and other regulatory experts expect the White House to send the final rule to Congress as early as late April and no later than May 22.

Either way, Tim Stenzel, MD, PhD, former director of the FDA’s Office of In Vitro Diagnostics, and other regulatory experts will be on hand at Executive War College (EWC) to walk attendees through what promises to be a “perfect storm of clinical lab and pathology practice regulatory changes.” Stenzel is scheduled to speak about the LDT rule during three sessions with fellow panelists on Day 1.

On Tuesday morning, Lâle White, executive chair and CEO of San Diego’s XiFin, Inc., will present a keynote on new regulations and diagnostics players that are “poised to reshape lab testing.” Her presentation is followed by a general session on Clinical Laboratory Improvement Amendments (CLIA) regulations featuring Salerno Reynolds, PhD., acting director at the U.S. Centers for Disease Control and Prevention (CDC) Center for Laboratory Systems and Response.

Robert Michel, Editor-in-Chief of The Dark Report will wrap day one with a general session on the regulatory trifecta coming soon to all labs, from LDT to CLIA to private payers’ policies for genetic claims.


Innovation in the spotlight

“It’s a rich mix of expert speakers, lab leaders who are doing innovative things in their own organizations, along with the consultants and the lab vendors who are pushing the front edge of laboratory management, operations, and clinical service delivery,” says Michel, who each year creates the agenda for EWC.

Several sessions, master classes, and speakers will look to the future with discussions about how healthcare data drives innovations in diagnostics and patient care, digital pathology adoption around the world, and hot topics such as artificial intelligence (AI), big data and precision medicine.

Panels offer a variety of viewpoints

“One valuable benefit of participating at the Executive War College is the various panel discussions,” Michel says. “Each panel brings together national experts in a specific area of the laboratory profession. As an example, our lab legal panel this year brings together four prominent and experienced attorneys who share opinions, insights, and commentary about relevant issues in compliance, regulations, and contractual issues with health plans and others.”

This allows attendees to experience a breadth of opinions from multiple respected experts in this area, he adds.

For example, a digital pathology panel will bring together representatives from labs, service providers, and the consultants that are helping labs implement digital pathology. The session will be especially helpful to labs that are deciding when to acquire digital pathology tools and how to deploy them effectively to improve diagnostic accuracy, Michel says.

And a managed care panel will feature executives from some of the nation’s biggest health plans—the ones that sit on the other side of the table from labs—to provide insights and guidance on how labs can work more effectively with them.

Networking opportunities abound

The event is about much more than politics and policy, however. There’s also a distinct social aspect.

“This is a friendly tribe,” Vicki DiFrancesco, a US HealthTek advisory board member who first attended EWC more than two decades ago, wrote in a recent post.

“Everyone is welcome, and everyone appreciates the camaraderie, so don’t be shy about going up and introducing yourself to someone. The quality of the crowd is top-notch, yet I’ve always experienced a willingness for those of us who have been to this rodeo to always be welcoming,” she notes.

Michel agrees. “One of the special benefits of participation at the EWC is the superb networking interactions and collaboration that takes place,” he says.

 “From the first moments that attendees walk into our opening reception on Monday night until the close of the optional workshops on Thursday, one can see a rich exchange happening amongst circles of attendees. Introductions are being made. Connections are developing into business opportunities. The sum of an attendee’s experience at the Executive War College is to gain as much knowledge from the networking and collaboration as they do from the sessions.”

–Gienna Shaw

Artificial Intelligence in the Operating Room: Dutch Scientists Develop AI Application That Informs Surgical Decision Making during Cancer Surgery

Speedy DNA sequencing and on-the-spot digital imaging may change the future of anatomic pathology procedures during surgery

Researchers at the Center for Molecular Medicine (CMM) at UMC Utrecht, a leading international university medical center in the Netherlands, have paired artificial intelligence (AI) and machine learning with DNA sequencing to develop a diagnostic tool cancer surgeons can use during surgeries to determine in minutes—while the patient is still on the operating table—whether they have fully removed all the cancerous tissue.

The method, “involves a computer scanning segments of a tumor’s DNA and alighting on certain chemical modifications that can yield a detailed diagnosis of the type and even subtype of the brain tumor,” according to The New York Times, which added, “That diagnosis, generated during the early stages of an hours-long surgery, can help surgeons decide how aggressively to operate, … In the future, the method may also help steer doctors toward treatments tailored for a specific subtype of tumor.”

This technology has the potential to reduce the need for frozen sections, should additional development and studies confirm that it accurately and reliably shows surgeons that all cancerous cells were fully removed. Many anatomic pathologists would welcome such a development because of the time pressure and stress associated with this procedure. Pathologists know that the patient is still in surgery and the surgeons are waiting for the results of the frozen section. Most pathologists would consider fewer frozen sections—with better patient outcomes—to be an improvement in patient care.

The UMC Utrecht scientist published their findings in the journal Nature titled, “Ultra-Fast Deep-Learned CNS Tumor Classification during Surgery.”

 “It’s imperative that the tumor subtype is known at the time of surgery,” Jeroen de Ridder, PhD (above), associate professor in the Center for Molecular Medicine at UMC Utrecht and one of the study leaders, told The New York Times. “What we have now uniquely enabled is to allow this very fine-grained, robust, detailed diagnosis to be performed already during the surgery. It can figure out itself what it’s looking at and make a robust classification,” he added. How this discovery affects the role of anatomic pathologists and pathology laboratories during cancer surgeries remains to be seen. (Photo copyright: UMC Utrecht.)

Rapid DNA Sequencing Impacts Brain Tumor Surgeries

The UMC Utrecht scientists employed Oxford Nanopore’s “real-time DNA sequencing technology to address the challenges posed by central nervous system (CNS) tumors, one of the most lethal type of tumor, especially among children,” according to an Oxford Nanopore news release.

The researchers called their new machine learning AI application the “Sturgeon.”

According to The New York Times, “The new method uses a faster genetic sequencing technique and applies it only to a small slice of the cellular genome, allowing it to return results before a surgeon has started operating on the edges of a tumor.”

Jeroen de Ridder, PhD, an associate professor in the Center for Molecular Medicine at UMC Utrecht, told The New York Times that Sturgeon is “powerful enough to deliver a diagnosis with sparse genetic data, akin to someone recognizing an image based on only 1% of its pixels, and from an unknown portion of the image.” Ridder is also a principal investigator at the Oncode Institute, an independent research center in the Netherlands.

The researchers tested Sturgeon during 25 live brain surgeries and compared the results to an anatomic pathologist’s standard method of microscope tissue examination. “The new approach delivered 18 correct diagnoses and failed to reach the needed confidence threshold in the other seven cases. It turned around its diagnoses in less than 90 minutes, the study reported—short enough for it to inform decisions during an operation,” The New York Times reported.

But there were issues. Where the minute samples contain healthy brain tissue, identifying an adequate number of tumor markers could become problematic. Under those conditions, surgeons can ask an anatomic pathologist to “flag the [tissue samples] with the most tumor for sequencing, said PhD candidate Marc Pagès-Gallego, a bioinformatician at UMC Utrecht and a co-author of the study,” The New York Times noted. 

“Implementation itself is less straightforward than often suggested,” Sebastian Brandner, MD, a professor of neuropathology at University College London, told The Times. “Sequencing and classifying tumor cells often still required significant expertise in bioinformatics as well as workers who are able to run, troubleshoot, and repair the technology,” he added. 

“Brain tumors are also the most well-suited to being classified by the chemical modifications that the new method analyzes; not all cancers can be diagnosed that way,” The Times pointed out.

Thus, the research continues. The new method is being applied to other surgical samples as well. The study authors said other facilities are utilizing the method on their own surgical tissue samples, “suggesting that it can work in other people’s hands.” But more work is needed, The Times reported.

UMC Utrecht Researchers Receive Hanarth Grant

To expand their research into the Sturgeon’s capabilities, the UMC Utrecht research team recently received funds from the Hanarth Fonds, which was founded in 2018 to “promote and enhance the use of artificial intelligence and machine learning to improve the diagnosis, treatment, and outcome of patients with cancer,” according to the organization’s website.

The researchers will investigate ways the Sturgeon AI algorithm can be used to identify tumors of the central nervous system during surgery, a UMC Utrecht news release states. These type of tumors, according to the researchers, are difficult to examine without surgery.

“This poses a challenge for neurosurgeons. They have to operate on a tumor without knowing what type of tumor it is. As a result, there is a chance that the patient will need another operation,” said de Ridder in the news release.

The Sturgeon application solves this problem. It identifies the “exact type of tumor during surgery. This allows the appropriate surgical strategy to be applied immediately,” the news release notes.

The Hanarth funds will enable Jeroen and his team to develop a variant of the Sturgeon that uses “cerebrospinal fluid instead of (part of) the tumor. This will allow the type of tumor to be determined already before surgery. The main challenge is that cerebrospinal fluid contains a mixture of tumor and normal DNA. AI models will be trained to take this into account.”

The UMC Utrecht scientists’ breakthrough is another example of how organizations and research groups are working to shorten time to answer, compared to standard anatomic pathology methods. They are combining developing technologies in ways that achieve these goals.

—Kristin Althea O’Connor

Related Information:

Ultra-fast Deep-Learned CNS Tumor Classification during Surgery

New AI Tool Diagnoses Brain Tumors on the Operating Table

Pediatric Brain Tumor Types Revealed Mid-Surgery with Nanopore Sequencing and AI

AI Speeds Up Identification Brain Tumor Type

Four New Cancer Research Projects at UMC Utrecht Receive Hanarth Grants

Rapid Nanopore Sequencing, Machine Learning Enable Tumor Classification during Surgery

Swiss Research Study into Long COVID Promises New Diagnostic and Therapeutic Possibilities

New biomarker may lead to new clinical laboratory testing and treatments for long COVID

Researchers studying long COVID at the University Hospital of Zurich (UZH) and the Swiss Institute of Bioinformatics (SIB), both in Switzerland, have discovered a protein biomarker in blood that indicates a component of the body’s innate immune system—called the complement system—remains active in some individuals long after the infection has run its course. The scientists are hopeful that further studies may provide clinical laboratories with a definitive test for long COVID, and pharma companies with a path to develop therapeutic drugs to treat it.

Ever since the COVID-19 pandemic began, a subset of the population worldwide continues to experience lingering symptoms even after the acute phase of the illness has passed. Patients with long COVID experience symptoms for weeks, even months after the initial viral infection has subsided. And because these symptoms can resemble other illnesses, long COVID is difficult to diagnose. 

This new biomarker may lead to new clinical laboratory diagnostic blood tests for long COVID, and to a greater understanding of why long COVID affects some patients and not others.

The Swiss scientists published their findings in the journal Science titled, “Persistent Complement Dysregulation with Signs of Thromboinflammation in Active Long COVID.”

“Those long COVID patients used to be like you and me, totally integrated [into] society with a job, social life, and private life,” infectious disease specialist Michelè van Vugt, MD (above), Senior Fellow and Professor at Amsterdam Institute for Global Health and Development (AIGHD), told Medical News Today. “After their COVID infection, for some of them, nothing was left because of their extreme fatigue. And this happened not only in one patient but many more—too many for only [a] psychological cause.” Clinical laboratories continue to perform tests on patients experiencing symptoms of COVID-19 even after the acute illness has passed. (Photo copyright: AIGHD.)

Role of the Complement System

To complete their study, the Swiss scientists monitored 113 patients who were confirmed through a reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test to have COVID-19. The study also included 39 healthy control patients who were not infected.

The researchers examined 6,596 proteins in 268 blood samples collected when the sick patients were at an acute stage of the virus, and then again six months after the infection. They found that 40 of the patients who were sick with COVID-19 eventually developed symptoms of long COVID. Those 40 patients all had a group of proteins in their blood showing that the complement system of their immune system was still elevated even after recovering from the virus.

“Complement is an arm of the immune system that ‘complements’ the action of the other arms,” Amesh Adalja, MD, Adjunct Assistant Professor at Johns Hopkins Bloomberg School of Public Health, told Prevention, “Activities that it performs range from literally attacking the cell membranes of a pathogen to summoning the cells of other immune systems to the site of infection.”

In addition to helping bodies heal from injury and illness, the complement immune system also activates inflammation in the body—and if the complement system is activated for too long the patient is at risk for autoimmune disease and other inflammatory conditions.

This inflammation may cause microclots in patients. “These can block the blood vessels and lead to damage … That can cause premature cardiac events, dementia, respiratory failure, and renal failure,” infectious disease specialist Thomas Russo, MD, SUNY Distinguished Professor, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, told Prevention.

Brain Fog

To make matters worse for long COVID patients, a recent study published in Nature Neuroscience titled, “Blood-Brain Barrier Disruption and Sustained Systemic Inflammation in Individuals with Long COVID-Associated Cognitive Impairment,” found that nearly 50% of people who experience long COVID also experience a condition called Brain Fog (aka, mental fog or clouding of consciousness.)

Conducted by genetic scientists at Trinity College Dublin and St. James’ Hospital in Dublin, Ireland, the study “analyzed blood samples—specifically, serum and plasma—from 76 patients who were hospitalized with COVID-19 in March or April 2020, along with those from 25 people taken before the pandemic. The researchers discovered that people who said they had brain fog had higher levels of a protein in their blood called S100β [a calcium-binding protein] than people who didn’t have brain fog,” Prevention reported.

“S100β is made by cells in the brain and isn’t normally found in the blood. That suggests that the patients had a breakdown in the blood-brain barrier, which blocks certain substances from getting to the brain and spinal cord, the researchers noted,” Prevention reported.

“The scientists then did MRI scans with dye of 22 people with long COVID (11 of them who reported having brain fog), along with 10 people who recovered from COVID-19. They found that long COVID patients who had brain fog had signs of a leaky blood-brain barrier,” Prevention noted.

“This leakiness likely disrupts the integrity of neurons in the brain by shifting the delicate balance of materials moving into and out of the brain,” Matthew Campbell, PhD, Professor and Head of Genetics at Trinity College Dublin, told Prevention.

Interactions with Other Viruses

According to Medical News Today, the Swiss study results also suggest that long COVID symptoms could appear because of the reactivation of a previous herpesvirus infection. The patients in the study showed increased antibodies against cytomegalovirus, a virus that half of all Americans have contracted by age 40.

The link between long COVID and these other viruses could be key to developing treatment for those suffering with both illnesses. The antiviral treatments used for the herpesvirus could potentially help treat long COVID symptoms as well, according to Medical News Today.

“Millions of people across the planet have long COVID or will develop it,” Thomas Russo MD, Professor and Chief of Infectious Disease at the University at Buffalo in New York, told Prevention. “It’s going to be the next major phase of this pandemic. If we don’t learn to diagnose and manage this, we are going to have many people with complications that impact their lives for the long term.”

Long COVID won’t be going away any time soon, much like the COVID-19 coronavirus. But these two studies may lead to more effective clinical laboratory testing, diagnoses, and treatments for millions of people suffering from the debilitating condition.

—Ashley Croce

Related Information:

New Study Finds Potential Cause of Long COVID Symptoms—Experts Explain

Persistent Complement Dysregulation with Signs of Thromboinflammation in Active Long COVID

CDC: Long COVID or Post-COVID Conditions

Long COVID: Major Findings, Mechanisms and Recommendations

Long COVID Explanation in New Study Possibly Paves Way for Tests and Treatments

Scientists May Have Discovered Reason for Long COVID Brain Fog—Here’s Why It Matters

Blood–Brain Barrier Disruption and Sustained Systemic Inflammation in Individuals with Long COVID-Associated Cognitive Impairment

Could New Clues on How Long COVID Affects Immune System Lead to Treatment?

Increased Testing Demands from Physicians is Putting New Zealand Clinical Laboratories Under Severe Stress

Following the loss of its histology accreditation, pressure on APS laboratory continues to mount

Government-run healthcare systems around the world often under-invest as demand grows and new healthcare technologies enter clinical practice. One such example is taking place in New Zealand, where public pathology and medical laboratory services are under extreme stress as physician test orders exceed the ability of the island nation’s clinical laboratories to keep up.

“The escalating pressure is complicating what was already a very difficult rescue job at one of the country’s busiest labs—Community Anatomic Pathology Services (APS),” RNZ reported. In 2023, APS lost its histology accreditation after it came to light that lab workers were not only exposed to toxic chemical levels at the facility, but that patients were waiting weeks for test results to return from the lab.

This follows a 2021 report from consultants PricewaterhouseCoopers (PwC) to the Auckland District Health Board in which New Zealand health authorities received warnings to improve pathology systems.

“The service is in crisis mode and, without urgent investment … there is a real risk that it will fail. The changes required are of such urgency that it is recommended that they be placed at the top of the agenda,” the report reads, RNZ reported.

“The size of New Zealand’s economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar,” wrote Andrew Blair, CMInstD (above), then General Manager of Royston Hospital, Hastings, New Zealand, in an article he penned for Jpn Hosp, the journal of the Japan Hospital Association. “The tolerance of New Zealanders would be challenged if a government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population’s expectations are increasing. This is the challenging situation we face today.” For New Zealand’s clinical laboratories, the demand for testing is increasing annually as the country’s population grows. (Photo copyright: Blair Consulting.)

Increased Demand on APS Leads to Problems

Established in 2015, APS tests thousands of anatomic and tissue samples yearly and is utilized by approximately a third of NZ’s population, according to RNZ.

The big story, however, is that from 2022 to 2023 utilization increased by a third. “The overall increasing demand is greater than the capacity of the service,” Te Whatu Ora (Health New Zealand), the country’s publicly-funded healthcare system, told RNZ.

As planned care increased, public hospitals started outsourcing operations to private surgical centers. A domino effect ensued when all of those samples then made their way to APS. There was an “increased volume of private surgery being carried out by 600 specialists in the region and 2,000 general practitioners, with up to 450 histology cases a day,” RNZ noted, adding, “The backlog has hit turnaround times for processing samples, which had been deteriorating.”

To make matters even more dire, working conditions at the country’s clinical labs is unfavorable and deteriorating, with short staffing, outdated workspaces and equipment, and exposure to dangerous chemicals.

In “New Zealand Clinical Laboratories to Undergo Health and Safety Checks after Workers Contract Typhoid, Others Exposed to Chemicals,” Dark Daily covered how Health New Zealand recently ordered health and safety checks at multiple clinical laboratories in 18 districts across the country. The action is the result of safety issues detected after procedural discrepancies were discovered in separate labs and follows months of strikes by NZ medical laboratory workers seeking fair pay and safe working conditions.

“Conditions got so bad from 2019-2021 that workers were exposed to cancer-causing formaldehyde in cramped workspaces, and flammable chemicals were stored unsafely,” RNZ reported.

While pay increases and safety improvements have provided some relief, the memory of past incidences coupled with increasing delays continue to undermine confidence in New Zealand’s laboratory industry.

Patients Also at Risk Due to Long Delays in Test Results

“We recognize the concern and impact any delayed results can cause referrers and their patients,” Health New Zealand said in a statement, RNZ reported.

Nevertheless, a 2023 article in The Conversation noted that, “38,000 New Zealanders had been waiting longer than the four-month target for being seen by a specialist for an initial assessment.”

These backlogs can be especially deadly for cancer patients. In “Pathology Lab Shortages in New Zealand Are One Cause in Long Delays in Melanoma Diagnoses,” Dark Daily detailed how patients awaiting melanoma diagnoses are experiencing delays upwards of one month due to long waits for test results.

However, according to plastic surgeon and Melanoma Network of New Zealand (MelNet) Chair Gary Duncan, MBChB, FRACS, when patients return to their doctors for test results, those results often have not come back from the medical laboratory. Therefore, the physician cannot discuss any issues, which causes the patient to have to make another appointment or receive a melanoma diagnosis over the telephone, RNZ reported.

“Slow pathology services are unfair to patients. Such delays could result in the spreading of the melanoma to other parts of the body and require major surgery under anesthetic,” dermatologist Louise Reiche, MBChB, FRACS, told RNZ. “Not only will they suffer an extensive surgical procedure, but it could also shorten their life.”

Improvements at APS Underway

Changes are currently underway that may decrease the long delays in test results at New Zealand’s labs. “A business case was being done to set up an electronic ordering system to cut down on manual processing errors,” RNZ reported.

Additionally, “the situation is much improved due to dispersal of work around [the] city and country for now. The teamwork around the region has been a veritable lifesaver,” a source familiar with the work told RNZ.

Construction of a new lab for APS is also allegedly in the works. However, to date no announcement has been made, according to RNZ.

Time will tell if New Zealand’s government can repair its pathology system. News stories showcasing damage caused by lengthy delays in clinical laboratory test results—and the ensuing patient harm due to rationed care in general—continue to reveal the weakness in government-run healthcare systems.

—Kristin Althea O’Connor

Related Information:

Private Healthcare Pushing Auckland Labs to the Brink

Te Whatu Ora Pathology Service Provider Loses Accreditation

NZ’s Health System Has Been Under Pressure for Decades. Reforms Need to Think Big and Long-Term to Be Effective

Meeting Increased Demand

Eight-Week Wait for Skin Cancer Test Results Risking Lives-Doctors

Pathology Lab Shortages in New Zealand Are One Cause in Long Delays in Melanoma Diagnoses

Te Whatu Ora Tight-Lipped on New Auckland Pathology Lab

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