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Compared to Telehealth/Virtual Visits, In-person Genetics Counseling Leads to Higher Clinical Lab Test Completion Rates, Study Shows

Research shows face-to-face genetics counseling overcomes barriers to proceeding with genetic testing and increases chances of catching cancer early

Research funded by the Prostate Cancer Foundation (PCF) has found that when patients receive in-person genetics counseling instead of virtual telehealth consultation, they are more likely to complete full germline genetic testing.

Clinical laboratory professionals have long been aware, at least anecdotally, that when physicians hand medical laboratory test orders to patients, a high percentage do not follow through and provide blood specimens for testing.

According to a PCF press release, with an on-site genetics counseling program “genetic testing occurs at the time of the consult,” whereas “with the telegenetics model, testing kits are mailed to the veteran’s home to be completed later, which can be a significant barrier, particularly for veterans with unstable housing. Researchers also explain that a face-to-face interaction with a trusted healthcare provider may be a better forum for having psychosocially complex genetic counseling discussions than telemedicine.”

This insight may be useful for genetic testing labs that can arrange for personal counseling of patients whose physician has recommended a complete full germline genetic test. Those labs would likely see a higher proportion of genetic test referrals convert into actual tests because more patients would decide to proceed.

The researchers published their findings in the journal JCO Oncology Practice, titled, “On-Site Nurse-Led Cancer Genetics Program Increases Cancer Genetic Testing Completion in Black Veterans.”

“Without a doubt, telemedicine has many benefits, but this research shows that when it comes to genetic counseling and testing, in-person consults are most impactful,” Howard R. Soule, PhD, PCF Executive Vice President and Chief Science Officer, said in the press release.

Prostate Cancer Foundation Executive Vice President and Chief Science Officer Howard R. Soule, PhD said in-person counseling for genetic testing is more effective than a telehealth consult. Clinical laboratories are familiar with the problem of patients not following through on doctors’ orders for lab testing. (Photo copyright: Prostate Cancer Foundation.)

Study Methodology and Results

The PCF conducted its retrospective study on 238 patients at the Corporal Michael J. Crescenz Veterans Department of Veterans Affairs Medical Center in Philadelphia. Oncologist Kara Maxwell, MD, PhD, Assistant Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, led the study.

Germline genetic testing identifies inherited mutations that may be linked to cancer. In at-risk individuals, it plays a role in secondary screening, and it is also an element in treating prostate and other cancers.

The patients in the study were referred for cancer genetics services between October 1, 2020, and February 28, 2022, the JCO Oncology Practice paper noted. About two-thirds (65%) were referred due to a personal history of cancer and 26% due to family history of cancer. More than half self-identified as Black.

Among the 238 patients, 130 received telehealth genetic counseling compared with 108 who were counseled onsite. A total of 117 patients in the study underwent the genetic testing.

The researchers found that among all patients in the study, those who received on-site counseling had a 3.2-fold higher likelihood of completing the genetic testing compared with the telehealth service. Among the patients who self-identified as Black, the likelihood was 4.8-fold higher. The study also found that those who received on-site counseling were less likely to miss follow-up care.

The study noted some demographic differences between the two groups: Veterans seen onsite had a median age of 71 and 92% were male. Among those who received telegenetics counselling, the median age was 57 and 58% were male.

Barriers to Genetic Testing

“Barriers to genetic testing—such as lack of access to cancer genetic services and an overall shortage of genetics service providers, both within and outside of the VA—translate to missed opportunities to diagnose cancer earlier, identify at risk family members, and offer precision oncology treatment,” the press release states.

Citing previous studies, the researchers noted that barriers to completion of genetic testing “have been magnified among racial minorities, even in cases for which there is a clear indication for testing, or if the testing is provided free of cost.”

One goal of the study, the researchers wrote, was to determine if on-site consultation could help overcome those barriers.

These consultations “can be complex encounters, and for patients with active cancer, they occur during a stressful period of their care,” the researchers wrote. The consults should include “the benefits and limitations of testing, different types of test results, and the risk of psychological impact of test results.”

Possible Explanations for Genetic Test Completion Rates

The researchers pointed to several possible explanations for the differences in testing rates. The on-site genetics nurse “has flexibility to see patients in the same physical space as their oncology follow-up or treatment visits.” The study found that this led to better attendance at appointments.

In addition, those patients received testing during the consultation. However, patients who underwent genetics counselling received their testing kits by mail. “This time delay allows for multiple intervening factors that could affect the completion of genetic testing,” the researchers wrote.

The researchers also suggested that patients may be more inclined to trust providers with whom they have face-to-face interactions.

“Our findings suggest that the presence of an on-site genetics service can potentially mitigate [racial] disparities, while effectively increasing the proportion of completed [genetic tests] for patients regardless of racial or ethnic background,” they wrote.

“Although telegenetics has greatly expanded access to genetics evaluations, it is possible that a face-to-face interaction with a provider onsite may be a better method for delivery of genetics consultations, given the inherent complexity in these encounters, particularly in the veteran population,” the researchers noted in JCO Oncology Practice. “It is imperative to optimize these interactions and facilitate genetics services follow-up, as the ultimate results from testing—if indicated—have profound implications on matters that are important to patients.”

Though the PCF study is confined to genetic testing and does not encompass all clinical laboratory testing, those with experience in medical laboratories know a high percentage of patients do not complete doctor-ordered lab tests.

“Going as far back as the 1990s, there has been recognition among pathologists and clinical laboratory managers that, as a rule of thumb, for every 100 lab test orders a doctor hands to patients, only 60% of those patients come in and provide a blood specimen,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report. “To my knowledge, there’s never been a published study about this aspect of clinical laboratory testing that has appeared in a peer-reviewed medical journal.

“Over the years, fear of needles was believed to be one reason why some patients accept a lab test order from their physician but do not take the next step of providing a specimen to a clinical lab,” Michel added. “Today, with high-deductible health plans and expensive genetic tests, cost would be another reason why patients might decline to go forward with lab tests ordered by their physicians.”

—Stephen Beale

Related Information:

On-Site Genetic Testing Consults Lead to Higher Testing Completion Rate, Finds PCF-Backed Study

Prostate Cancer Foundation-Funded Study Sheds Light on Improving Access to Precision Oncology Care for US Veterans with Prostate Cancer

On-Site Nurse-Led Cancer Genetics Program Increases Cancer Genetic Testing Completion in Black Veterans

Providers and Legislators Seek Changes in Rules Implementing No Surprises Act and How Physicians, Labs, and Other Providers Can Bill Patients

Provider groups and members of Congress say the rules favor payers, federal judge agrees, but path forward in how providers bill patients remains unclear

Groups representing healthcare providers—including pathologists—are challenging the Biden administration’s implementation of the No Surprises Act, a bill passed in 2020 that aims to protect patients from surprise medical bills.

This will be of particular interest to pathologists who—as a study from the Health Care Cost Institute (HCCI) found—were second only to emergency room physicians among providers with the highest percentage of out-of-network billing.

Dark Daily’s sister publication The Dark Report covered the HCCI study and its findings in “Federal Rule to Revise Out-Of-Network Billing.”

The College of American Pathologists (CAP) and American Society for Clinical Pathology (ASCP), both of which supported the No Surprises Act, are now among numerous provider groups claiming that the bill’s rules for resolving payment disputes unfairly favor payers.

These groups have bipartisan support in Congress, Bloomberg Law reported, noting that some legislators are urging Health and Human Services (HHS) Secretary Xavier Becerra to change the rules. The lawmakers may seek to amend the law or turn to the courts if Becerra does not follow through on their requests.

“Either we legislate, we go to court, whatever it takes,” Rep. Brad Wenstrup (R-Ohio) told Bloomberg. Meanwhile, a federal district court judge has sided with the Texas Medical Association (TMA) in two lawsuits over the rules, Healthcare Dive reported.

“We need to make sure that the administration is implementing what we passed consistent with the legislative intent,” Sen. Michael Bennet (D-Colorado) told Bloomberg Law regarding the No Surprises Act. “We had a very complicated coalition of people to come together to support this legislation.” (Photo copyright: Senate.gov.)

Details of No Surprises Act

The No Surprises Act aims to protect patients from “balance billing,” in which they receive surprise bills for out-of-network medical services even when they use in-network providers. The bill was signed into law in December 2020, with most provisions taking effect on Jan. 1, 2022.

As Dark Daily reported in “ASCP and CAP Support New Legislation That Bars Surprise Medical Billing,” following passage of the bill, patients who unknowingly receive services from out-of-network providers are liable only for costs they would have incurred for in-network care. Providers and payers then have 30 days to negotiate a payment. If they can’t agree, an arbiter determines the payment as part of a federal independent dispute resolution (IDR) process.

Passage of the bill required the federal Department of Health and Human Services (HHS), Department of Treasury, and Department of Labor to craft regulations and guidance to implement the law—including the IDR process—according to the American Hospital Association (AHA).

Legal Pushback to Arbitration Rule

One contention was an interim rule that instructed arbiters to use the “qualifying payment amount” (QPA) as the primary basis for ruling in favor of either insurers or providers in payment disputes.

Writing in MedPage Today, pediatric radiologist Richard Heller, MD, National Subspecialty Lead for Pediatric Radiology at Radiology Partners in Chicago, and Radiological Society of North America (RSNA) Board Liaison for Public Information and Corporate Relations, described the QPA as “the insurer’s median in-network rate.”

Heller wrote that “the calculation methodology does not result in real world, market-based rates. Further, insurers calculate their own QPA, and may do so in a non-transparent fashion, raising questions about QPA integrity.”

He added, “The departments have repeatedly tried to establish the QPA as the primary factor arbiters should use in their decision making. These attempts have twice been rejected by a federal court. Recent guidance issued by the administration as a result of the second Texas Medical Association lawsuit more closely reflects the balance that Congress intended.”

In its first lawsuit, the TMA characterized the QPA as “an opaque and flawed insurer-calculated amount” that would result in reduced payments to providers. The lawsuit claimed that Congress, instead, intended for the dispute resolution process to look at “a range of factors.”

Federal Judge Jeremy Kernodle ruled in the TMA’s favor and ordered HHS to change the rule. He also sided with the TMA in another lawsuit, which alleged that a final rule issued in August 2022, while “formally abandoning the QPA rebuttable presumption,” unduly restricted use of non-QPA factors, according to a litigation update for certified IDR entities from Sidley Austin LLP.

The final rule “nevertheless continues to place a thumb on the scale for the QPA by requiring arbitrators to begin with the QPA and then imposing restrictions on the non-QPA factors that appear nowhere in the statute,” the judge stated in his ruling, the American Medical Association (AMA) reported.

In its latest lawsuit, the TMA is challenging a big hike in administrative fees for dispute resolution, which went from $50 initially to $350 beginning last January.

Another issue with the law has been the sheer volume of arbitration cases. The administration originally estimated that payers and providers would submit about 17,000 claims per year, but between April 15 and Sept. 30, 2022, about 90,000 disputes were initiated, according to a government report cited by RevCycleIntelligence.

The No Surprises Act reflected lawmaker compromises about arbitration, Sen. Michael Bennet (D-Colorado) told Bloomberg Law. Bennet indicated to the news outlet that he is not happy with the current arbitration process.

Pathology Groups Weigh In

The CAP and ASCP joined other physician organizations in raising early objections to the Biden Administration’s plans to implement the independent dispute process.

“The skewed IDR process outlined within the IFC [Interim Final Rule with Comment Period] will remove a critical incentive for insurers to negotiate reasonable contracts with physicians by establishing the QPA as a reasonable out-of-network payment,” the ASCP stated in a Dec. 6, 2021, letter to administration officials.

On Dec. 23, 2021, the CAP filed an amicus brief in a lawsuit brought by the AMA and AHA challenging an interim rule issued that September. The regulations “must support an equitable and balanced system for resolving out-of-network payment disputes,” said CAP President Emily Volk, MD, FCAP in a statement accompanying the filing. “As of today, the rules heavily favor the insurers when their power is already too great.”

The AMA and AHA later withdrew the lawsuit after the Biden administration revised the rule, Healthcare Finance News reported. However, the groups still contend that the rule favors payers.

High Stakes for Pathologists

When the law passed Congress, it appeared likely it would have a disproportionate impact on medical laboratories and pathology groups. The HCCI report ranked pathology number two among six specialties responsible for the highest percentage of out-of-network bills. And when the interim final rule was published in the Federal Register, the HCCI data was cited in an accompanying commentary.

However, the CAP told The Dark Report that the statistics about pathologists, though accurate, were “presented in a somewhat misleading manner.”

The No Surprises Act does permit balance billing when patients have given prior consent, but pathologists were among a group of specialties barred entirely from the practice, Dark Daily previously reported.

—Stephen Beale

Related Information:

Surprise Medical Bill Disputes Spur Lawmakers to Seek Changes

The Six Provider Lawsuits Over the No Surprises Act: Latest Developments

HCCI: How Often Do Providers Bill Out of Network?

HHS and Federal Departments Issue Final Rules to Clarify No Surprises Act Dispute Resolution

Biden Administration Should Revise No Surprises Act Rules, Says ASCP

Judge Removes Disputed Element of No Surprises Act

Southern California Physician and Clinical Laboratory Owners Charged in Federal Crackdown on Pandemic-Related Billing Fraud

Federal prosecutors build the new healthcare-related fraud cases on previous nationwide enforcement actions from 2022

Federal charges have once again been brought against a number of physicians and clinical laboratory owners in what the US Department of Justice described as the “largest ever” coordinated nationwide law enforcement effort against COVID-19 pandemic-related healthcare fraud.

In total, the DOJ filed criminal charges against 18 defendants in five states plus the territory of Puerto Rico, according to an April 20 press release.

The highest dollar amount of these frauds involved ENT physician Anthony Hao Dinh, DO, who allegedly defrauded the Health Resources and Services Administration (HRSA) COVID-19 Uninsured Program for millions of dollars, and Lourdes Navarro, owner of Matias Clinical Laboratory, for allegedly “submitting over $358 million in false and fraudulent claims to Medicare, HRSA, and a private insurance company for laboratory testing” while performing “COVID-19 screening testing for nursing homes and other facilities with vulnerable elderly populations, as well as primary and secondary schools,” the press release states. Both court cases are being conducted in Southern California courtrooms.

The DOJ’s filing of charges came rather speedily, compared to other cases involving fraudulent clinical laboratory testing schemes pre-pandemic. The amount of money each defendant managed to generate in reimbursement from the fraud represents tens of thousands of patients. If feds were paying $100 per COVID-19 test, then the $153 million represents 153,000 patients, in just 18 to 24 months.

Assistant Attorney General Kenneth A. Polite, Jr.

“Today’s announcement marks the largest-ever coordinated law enforcement action in the United States targeting healthcare fraud schemes that exploit the COVID-19 pandemic,” said Assistant Attorney General Kenneth A. Polite, Jr. (above), in an April 20 DOJ press release. “The Criminal Division’s Health Care Fraud Unit and our partners are committed to rooting out pandemic-related fraud and holding accountable anyone seeking to profit from a public health emergency.” Clinical laboratory managers may want to pay close attention to the DOJ’s prosecution of these newest cases of alleged COVID-19 fraud. (Photo copyright: Department of Justice.)

Matias Clinical Laboratory, Inc.

The DOJ first brought fraud charges against Lourdes Navarro, owner of Matias Clinical Laboratory (Matias) in Baldwin Park, California, in April 2022. The Dark Daily covered that federal crackdown in “California Clinical Laboratory Owners among 21 Defendants Indicted or Criminally Charged for COVID-19 Test Fraud and Other Schemes Totaling $214 Million.

Then, in April of 2023, the DOJ filed expanded charges against the 18 defendants, including the owners of Matias which provided COVID-19 screening for schools, rehab facilities, and eldercare facilities, according to a United States Attorney’s Office, Central District of California press release.

Prosecutors allege that Navarro and her husband, Imran Shams, who operated Matias—also known as Health Care Providers Laboratory—perpetrated a scheme to perform medically unnecessary respiratory pathogen panel (RPP) tests on specimens collected for COVID-19 testing, even though physicians had not ordered the RPP tests and the specimens were collected from asymptomatic individuals.

In some cases, the indictment alleges, Navarro and Shams paid kickbacks and bribes to obtain the samples.

The indictment notes that reimbursement for RPP and other respiratory pathogen tests is generally “several times higher” than reimbursement for COVID-19 testing. Claims for the tests were submitted to Medicare and an unidentified private insurer, as well as the HRSA COVID-19 Uninsured Program, which provided support for COVID-19 testing and treatment for uninsured patients.

Claims to the HRSA falsely represented that “the tested individuals had been diagnosed with COVID-19, when in truth and in fact, the individuals had not been diagnosed with COVID-19 and the tests were for screening purposes only,” the First Superseding Indictment states.

The indictment further states that both Navarro and Shams had previously been barred from participating in Medicare and other federal healthcare programs due to past fraud convictions. Navarro, the indictment alleges, was reinstated in December 2018 after submitting a “false and fraudulent” application to the HHS Office of Inspector General.

It also alleges that Navarro and Shams concealed their ownership role in Matias so the lab could maintain billing privileges.

More Alleged Abuse of HRSA Uninsured Program

In a separate case, Federal prosecutors alleged that Anthony Hao Dinh, DO, an ear, nose, and throat physician in Orange County, California, engaged in a scheme to defraud the HRSA COVID-19 Uninsured Program as well.

Dinh, prosecutors allege, “submitted fraudulent claims for treatment of patients who were insured, billed for services that were not rendered, and billed for services that were not medically necessary.”

The criminal complaint, filed on April 10, alleges that Dinh submitted claims for approximately $230 million, enough to make him the program’s second-highest biller. He was paid more than $153 million, prosecutors allege, and “used fraud proceeds for high-risk options trading, losing over $100 million from November 2020 through February 2022,” states the US Attorney’s Office, Central District of California press release.

Dinh was also charged for allegedly attempting to defraud the federal Paycheck Protection Program (PPP) and Economic Injury Disaster Loan (EIDL) program. He faces a maximum sentence of 50 years in federal prison, the press release states.

Dinh’s sister, Hang Trinh Dinh, 64, of Lake Forest, California, and Matthew Hoang Ho, 65, of Melbourne, Florida, are also charged in the complaint, the Los Angeles Times reported.

Both of these cases are notable because of the size of the fraud each defendant pulled off involving COVID-19 lab testing. Clinical laboratory managers may want to review the original court indictments. The documents show the brazenness of these fraudsters and detail how they may have induced other doctors to refer them testing specimens.

Stephen Beale

Related Information:

Justice Department Announces Nationwide Coordinated Law Enforcement Action to Combat COVID-19 Health Care Fraud

DOJ Announces Nationwide Coordinated Law Enforcement Action to Combat Health Care Fraud Related to COVID-19—Summary of Criminal Charges

Criminal Complaint: US v. Dinh, et al.

Criminal Complaint: US v. Navarro

Newport Coast Physician Faces Federal Charges in Healthcare Fraud Cases

COVID Fraud Takedowns: Feds Charge 18 People, Including Doctors, with Raking in Nearly $500M from Scams

California Clinical Laboratory Owners among 21 Defendants Indicted or Criminally Charged for COVID-19 Test Fraud and Other Schemes Totaling $214 Million

UCSF Researchers Identify Genetic Mutation That Promotes an Asymptomatic Response in Humans to COVID-19 Infection

Understanding why some people display no symptoms during a COVID-19 infection could lead to new precision medicine genetic tests medical labs could use to identify people with the mutated gene

New research from the University of California San Francisco (UCSF) may explain why some people could get COVID-19 but never test positive on a clinical laboratory test or develop symptoms despite exposure to the SARS-CoV-2 coronavirus.

According to the UCSF study, variations in a specific gene in a system of genes responsible for regulating the human immune system appears to be the factor in why about 10% of those who become infected with the virus are asymptomatic.

These scientific insights did not receive widespread news coverage but will be of interest to clinical laboratory managers and pathologists who oversee SARS-CoV-2 testing in their labs.

Jill Hollenbach, PhD

“Some people just don’t have symptoms at all,” Jill Hollenbach, PhD (above), Professor of Neurology at UCSF’s Weill Institute for Neurosciences and lead researcher in the study, told NBC News. “There’s something happening at a really fundamental level in the immune response that is helping those people to just completely wipe out this infection.” Identifying a genetic reason why some people are asymptomatic could lead to new precision medicine clinical laboratory diagnostics for COVID-19. (Photo copyright: Elena Zhukova /University of California San Francisco.)

Fortunate Gene Mutation

According to the Centers for Disease Control and Prevention’s (CDC) COVID Data Tracker, as of April 5, 2023, a total of 104,242,889 COVID-19 cases have been reported in the United States. However, according to a CDC Morbidity and Mortality Weekly Report (MMWR), “Traditional methods of disease surveillance do not capture all COVID-19 cases because some are asymptomatic, not diagnosed, or not reported; therefore, [knowing the true] proportion of the population with SARS-CoV-2 antibodies (i.e., seroprevalence) can improve understanding of population-level incidence of COVID-19.”

Jill Hollenbach, PhD, lead researcher in the UCSF study and Professor of Neurology at UCSF’s Weill Institute for Neurosciences, runs the Hollenbach Lab at UCSF. The lab specializes in the study of two important elements in human immune response:

She also participates in the COVID-19 HLA and Immunogenetics Consortium, a group of academic researchers, clinical laboratory directors, journal editors, and others who examine the role of HLA variations in determining COVID-19 risk.

Hollenbach’s research identified an HLA variant—known as HLA-B*15:01—that causes the human immune system to react quickly to SARS-CoV-2 and “basically nuke the infection before you even start to have symptoms,” she told NPR.

“It’s definitely luck,” she added. “But, you know, this [gene] mutation is quite common. We estimate that maybe one in 10 people have it. And in people who are asymptomatic, that rises to one in five.”

The researchers published their findings on the medRxiv preprint server titled, “A Common Allele of HLA Mediates Asymptomatic SARS-CoV-2 Infection.” The UCSF study has not yet been peer-reviewed.

UCSF Study Methodology

“HLA variants are among the strongest reported associations with viral infections,” the UCSF study notes. So, the researchers theorized that HLA variations play a role in asymptomatic SARS-CoV-2 infections as well.

To conduct their study, shortly after the SARS-CoV-2 outbreak in 2020, the researchers recruited approximately 30,000 volunteer bone marrow donors from the National Marrow Donor Program to respond to periodic questions via a smartphone app or website. Because HLA variations can determine appropriate matches between donors and recipients, the database includes information about their HLA types.

Each week, respondents were asked to report if they had been tested for SARS-CoV-2. Each day, they were asked to report whether they had symptoms associated with COVID-19. “We were pretty stringent in our definition of asymptomatic,” Hollenbach told NBC News. “[The respondents couldn’t] even have a scratchy throat.”

The researchers eventually identified a cohort of 1,428 people who had tested positive for SARS-CoV-2 between February 2020 and April 30, 2021, before vaccines were widely available. Among these individuals, 136 reported no symptoms for two weeks before or two weeks after a positive test.

“Overall, one in five individuals (20%) who remained asymptomatic after infection carried HLA-B*15:01, compared to 9% among patients reporting symptoms,” the researchers wrote in their medRxiv preprint. Study participants with two copies of the gene were more than eight times more likely to be asymptomatic.

The UCSF researchers also looked at four other HLA variants and found none to be “significantly associated” with lack of symptoms. They confirmed their findings by reproducing the HLA-B association in two additional independent cohorts, one from an earlier study in the UK and the other consisting of San Francisco-area residents.

Individuals in the latter group had either tested positive for SARS-CoV-2 or reported COVID symptoms, and their DNA was analyzed to determine their HLA types.

Pre-existing T-Cell Immunity May Reduce Severity of COVID-19 Infection

The UCSF researchers also attempted to determine how HLA-B*15:01 plays a role in knocking out SARS-CoV-2 infections. They noted previous research that indicated previous exposure to seasonal coronaviruses, such as common cold viruses, could limit the severity of COVID-19. The scientists hypothesized that pre-existing T-cell immunity in HLA-B carriers may be the key.

The COVID-19 HLA and Immunogenetics Consortium website describes how HLA and T-cells work together to ward off disease. HLA “proteins are found on the surface of all cells except red-blood cells.” They’re “like windows into the inner workings of a cell,” and T-cells use the molecules to determine the presence of foreign proteins that are likely signs of infection. “Activated T-cells can kill infected cells, or activate B-cells, which produce antibodies in response to an infection,” the website explains.  

Hollenbach’s research team analyzed T-cells from pre-pandemic individuals and observed that in more than half of HLA-B carriers, the T-cells were reactive to a SARS-CoV-2 peptide. The scientists corroborated the hypothesis by examining crystal structures of the HLA-B*15:01 molecule in the presence of coronavirus spike peptides from SARS-CoV-2 and two other human coronaviruses: OC43-CoV and HKU1-CoV.

“Altogether, our results strongly support the hypothesis that HLA-B*15:01 mediates asymptomatic COVID-19 disease via pre-existing T-cell immunity due to previous exposure to HKU1-CoV and OC43-CoV,” the researchers wrote.

Can Genes Prevent COVID-19 Infections?

Meanwhile, researchers at The Rockefeller University in New York City are attempting to go further and see if there are mutations that prevent people from getting infected in the first place. NPR reported that they were seeking participants for a study seeking to identify so-called “superdodger” genes.

“You fill out a questionnaire online about your exposures to SARS-CoV-2,” explained Jean-Laurent Casanova, MD, PhD, professor, senior attending physician, and head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University, who is leading the study.

Study participants identified as possibly having superdodger genes receive a kit designed to collect saliva samples, after which the researchers sequence the respondents’ genomes. “We hope that in a group of 2,000 to 4,000 people, some people will have genetic mutations that tell us why they’re resistant to infection,” Casanova told NPR.

All this genetic research is in very early stages. But results are promising and may lead to new precision medicine clinical laboratory tests for identifying people who are predisposed to having an asymptomatic response to COVID-19 infection. That in turn could help scientists learn how to moderate or even eliminate symptoms in those unfortunate people who suffer the typical symptoms of the disease.   

—Stephen Beale

Related Information:

A Common Allele of HLA Mediates Asymptomatic SARS-CoV-2 Infection

What People with ‘Super Immunity’ Can Teach Us about COVID and Other Viruses

So, You Haven’t Caught COVID Yet. Does That Mean You’re a Superdodger?

If You Haven’t Gotten COVID Yet, This Might Be Why

Trends in Number of COVID-19 Cases and Deaths in the US Reported to CDC, by State/Territory

UC San Francisco Researchers Discover Why Some People Are Asymptomatic When Infected with COVID-19

Seroprevalence of Infection-Induced SARS-CoV-2 Antibodies—United States, September 2021–February 2022

Scientists Revive and Characterize 13 Ancient “Zombie” Viruses Isolated from Siberian Permafrost

Viruses are between 27,000 to 48,500 years old and not dangerous, but researchers say thawing permafrost may one day release pathogens capable of infecting humans

Last fall, European researchers working with virologists and genetic scientists at the Aix-Marseille University in France reported having revived and characterized 13 previously unknown “zombie” viruses isolated from Siberian permafrost samples, including one that was almost 50,000 years old. This will be of particular interest to microbiologists and clinical laboratory managers since these organisms are new to science and may be precursors to infectious agents active in the world today.

The work of the European scientists demonstrates how advancements in genome sequencing and analysis of DNA data are becoming, faster, less expensive, and more precise. That’s good because the researchers warned that, should the permafrost continue to thaw, other previously dormant viruses could be released, posing potential risks for public health.

The scientists published their findings in the open-access journal Viruses titled, “An Update on Eukaryotic Viruses Revived from Ancient Permafrost.”

The pathogens isolated by the researchers are so-called “giant viruses” that infect Acanthamoeba, a commonly found genus of amoeba, and thus are not likely to pose an immediate health threat, the researchers wrote.

However, the scientists expressed concern. “We believe our results with Acanthamoeba-infecting viruses can be extrapolated to many other DNA viruses capable of infecting humans or animals. It is thus likely that ancient permafrost … will release these unknown viruses upon thawing,” they stated in their Viruses paper.

It’s unknown how long the viruses “could be infectious once exposed to outdoor conditions (UV light, oxygen, heat), and how likely they will be to encounter and infect a suitable host in the interval,” they added. However, “the risk is bound to increase in the context of global warming, in which permafrost thawing will keep accelerating, and more people will populate the Arctic in the wake of industrial ventures.”

Paulo Verardi, PhD

“In nature we have a big natural freezer, which is the Siberian permafrost,” virologist Paulo Verardi, PhD (above), head of the Department of Pathobiology and Veterinary Science at the University of Connecticut, told The Washington Post. “And that can be a little bit concerning.” However, “if you do the risk assessment, this is very low. We have many more things to worry about right now.” Nevertheless, clinical laboratories may want to remain vigilant. (Photo copyright: University of Connecticut.)

Extremely Old, Very Large Viruses

The newly discovered viruses were found in seven different permafrost samples. Radiocarbon dating determined that they had been dormant for 27,000 to 48,500 years. But viruses contained in permafrost could be even older, the researchers wrote, as the time limit is “solely dictated by the validity range of radiocarbon dating.”

In their Viruses paper, the researchers noted that most of the 13 viruses are “at a preliminary stage of characterization,” and others have been isolated in the research laboratory “but not yet published, pending their complete genome assembly, annotation, or detailed analysis.”

“Every time we look, we will find a virus,” study co-author Jean-Michel Claverie, PhD, told The Washington Post. “It’s a done deal. We know that every time we’re going to look for viruses—infectious viruses in permafrost—we are going to find some.”

Claverie is a professor emeritus of genomics and bioinformatics in the School of Medicine at Aix-Marseille Université in Marseille, France. He leads a university laboratory known for its work in “paleovirology,” and in 2003, discovered the first known giant virus, dubbed Mimivirus. The research team included scientists from Germany and Russia.

According to CNN, unlike regular viruses that generally require an electron microscope to be viewed, giant viruses can be seen under a standard light (optical) microscope. Claverie’s laboratory previously isolated giant viruses from permafrost in 2014 and 2015.

Protecting Against Accidental Infection

To demonstrate the infectious potential of the viruses, the researchers inserted the microbes into cultured amoeba cells, which the researchers describes as “virus bait,” The Washington Post reported. One advantage of using Acanthamoeba cultures is to maintain “biological security,” the researchers wrote in their paper.

“We are using [the amoeba’s] billion years of evolutionary distance with human and other mammals as the best possible protection against an accidental infection of laboratory workers or the spread of a dreadful virus once infecting Pleistocene mammals to their contemporary relatives,” the paper noted. “The biohazard associated with reviving prehistorical amoeba-infecting viruses is thus totally negligible compared to the search for ‘paleoviruses’ directly from permafrost-preserved remains of mammoths, woolly rhinoceros, or prehistoric horses.”

The paper cites earlier research noting the presence of bacteria in ancient permafrost samples, “a significant proportion of which are thought to be alive.” These include relatives of contemporary pathogens such as:

How Dangerous are Ancient Viruses?

“We can reasonably hope that an epidemic caused by a revived prehistoric pathogenic bacterium could be quickly controlled by the modern antibiotics at our disposal,” the researchers wrote, but “the situation would be much more disastrous in the case of plant, animal, or human diseases caused by the revival of an ancient unknown virus.”

However, according to The Washington Post, “Virologists who were not involved in the research said the specter of future pandemics being unleashed from the Siberian steppe ranks low on the list of current public health threats. Most new—or ancient—viruses are not dangerous, and the ones that survive the deep freeze for thousands of years tend not to be in the category of coronaviruses and other highly infectious viruses that lead to pandemics.”

Cornell University virologist Colin Parrish, PhD, President of the American Society for Virology, told The Washington Post that an ancient virus “seems like a low risk compared to the large numbers of viruses that are circulating among vertebrates around the world, and that have proven to be real threats in the past, and where similar events could happen in the future, as we still lack a framework for recognizing those ahead of time.”

Anthony Fauci, MD, former Director of the National Institute of Allergy and Infectious Diseases (NIAID), responded to an earlier study from Claverie’s lab by outlining all the unlikely events that would have to transpire for one of these viruses to cause a pandemic. “The permafrost virus must be able to infect humans, it must then [cause disease], and it must be able to spread efficiently from human to human,” he told The Washington Post in 2015. “This can happen, but it is very unlikely.”

Thus, clinical laboratories probably won’t see new diagnostic testing to identify ancient viruses anytime soon. But it’s always best to remain vigilant.

Stephen Beale

Related Information:

Scientists Have Revived a ‘Zombie’ Virus That Spent 48,500 Years Frozen in Permafrost

‘Zombie’ Viruses Are Thawing in Melting Permafrost Because of Climate Change

Ancient Dormant Viruses Found in Permafrost, Once Revived, Can Infect Amoeba

Scientists Revive 48,500-Year-Old ‘Zombie Virus’ Buried in Ice

Scientists Revived Ancient ‘Zombie Viruses’ Frozen for Eons in Siberia

Scientists Warn Long-Frozen ‘Zombie Virus’ Is ‘Public Health Threat’ Amid Thaw

Scientists Did Not Release a Zombie Plague by Reviving a Dormant Virus, but Their Warning of a Potential Public Health Crisis Is Legitimate

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