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Separate Reports Shed Light on Why CDC SARS-CoV-2 Test Kits Failed During Start of COVID-19 Pandemic

HHS Office of Inspector General was the latest to examine the quality control problems that led to distribution of inaccurate test to clinical laboratories nationwide

Failure on the part of the Centers for Disease Control and Prevention (CDC) to produce accurate, dependable SARS-CoV-2 clinical laboratory test kits at the start of the COVID-19 pandemic continues to draw scrutiny and criticism of the actions taken by the federal agency.

In the early weeks of the COVID-19 pandemic, the CDC distributed faulty SARS-CoV-2 test kits to public health laboratories (PHLs), delaying the response to the outbreak at a critical juncture. That failure was widely publicized at the time. But within the past year, two reports have provided a more detailed look at the shortcomings that led to the snafu.

The most recent assessment came in an October 2023 report from the US Department of Health and Human Services Office of Inspector General (OIG), following an audit of the public health agency. The report was titled, “CDC’s Internal Control Weaknesses Led to Its Initial COVID-19 Test Kit Failure, but CDC Ultimately Created a Working Test Kit.”

“We identified weaknesses in CDC’s COVID-19 test kit development processes and the agencywide laboratory quality processes that may have contributed to the failure of the initial COVID-19 test kits,” the OIG stated in its report.

Prior to the outbreak, the agency had internal documents that were supposed to provide guidance for how to respond to public health emergencies. However, “these documents do not address the development of a test kit,” the OIG stated.

Jill Taylor, PhD

“If the CDC can’t change, [its] importance in health in the nation will decline,” said microbiologist Jill Taylor, PhD (above), Senior Adviser for the Association of Public Health Laboratories in Washington, DC. “The coordination of public health emergency responses in the nation will be worse off.” Clinical laboratories that were blocked from developing their own SARS-CoV-2 test during the pandemic would certainly agree. (Photo copyright: Columbia University.)

Problems at the CDC’s RVD Lab

Much of the OIG’s report focused on the CDC’s Respiratory Virus Diagnostic (RVD) lab which was part of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD). The RVD lab had primary responsibility for developing, producing, and distributing the test kits. Because it was focused on research, it “was not set up to develop and manufacture test kits and therefore had no policies and procedures for developing and manufacturing test kits,” the report stated.

The RVD lab also lacked the staff and funding to handle test kit development in a public health emergency, the report stated. As a result, “the lead scientist not only managed but also participated in all test kit development processes,” the report stated. “In addition, when the initial test kit failed at some PHLs, the lead scientist was also responsible for troubleshooting and correcting the problem.”

To verify the test kit, the RVD lab needed samples of viral material from the agency’s Biotechnology Core Facility Branch (BCFB) CORE Lab, which also manufactured reagents for the kit.

“RVD Lab, which was under pressure to quickly create a test kit for the emerging health threat, insisted that CORE Lab deviate from its usual practices of segregating these two activities and fulfill orders for both reagents and viral material,” the report stated.

This increased the risk of contamination, the report said. An analysis by CDC scientists “did not determine whether a process error or contamination was at fault for the test kit failure; however, based on our interviews with CDC personnel, contamination could not be ruled out,” the report stated.

The report also cited the CDC’s lack of standardized systems for quality control and management of laboratory documents. Labs involved in test kit development used two different incompatible systems for tracking and managing documents, “resulting in staff being unable to distinguish between draft, obsolete, and current versions of laboratory procedures and forms.”

Outside Experts Weigh In

The OIG report followed an earlier review by the CDC’s Laboratory Workgroup (LW), which consists of 12 outside experts, including academics, clinical laboratory directors, state public health laboratory directors, and a science advisor from the Association of Public Health Laboratories. Members were appointed by the CDC Advisory Committee to the Director.

This group cited four major issues:

  • Lack of adequate planning: For the “rapid development, validation, manufacture, and distribution of a test for a novel pathogen.”
  • Ineffective governance: Three labs—the RVD Lab, CORE Lab, and Reagent and Diagnostic Services Branch—were involved in test kit development and manufacturing. “At no point, however, were these three laboratories brought together under unified leadership to develop the SARS-CoV-2 test,” the report stated.
  • Poor quality control and oversight: “Essentially, at the start of the pandemic, infectious disease clinical laboratories at CDC were not held to the same quality and regulatory standards that equivalent high-complexity public health, clinical and commercial reference laboratories in the United States are held,” the report stated.
  • Poor test design processes: The report noted that the test kit had three probes designed to bind to different parts of the SARS-CoV-2 nucleocapsid gene. The first two—N1 (topology) and N2 (intracellular localization)—were designed to match SARS-CoV-2 specifically, whereas the third—N3 (functions of the protein)—was designed to match all Sarbecoviruses, the family that includes SARS-CoV-2 as well as the coronavirus responsible for the 2002-2004 SARS outbreak.

The N1 probe was found to be contaminated, the group’s report stated, while the N3 probe was poorly designed. The report questioned the decision to include the N3 probe, which was not included in European tests.

Also lacking were “clearly defined pass/fail threshold criteria for test validation,” the report stated.

Advice to the CDC

Both reports made recommendations for changes at the CDC, but the LW’s were more far-reaching. For example, it advised the agency to establish a senior leader position “with major responsibility and authority for laboratories at the agency.” This individual would oversee a new Center that would “focus on clinical laboratory quality, laboratory safety, workforce training, readiness and response, and manufacturing.”

In addition, the CDC should consolidate its clinical diagnostic laboratories, the report advised, and “laboratories that follow a clinical quality management system should have separate technical staff and space from those that do not follow such a system, such as certain research laboratories.”

The report also called for collaboration with “high functioning public health laboratories, hospital and academic laboratories, and commercial reference laboratories.” For example, collaborating on test design and development “should eliminate the risk of a single point of failure for test design and validation,” the LW suggested.

CBS News reported in August that the CDC had already begun implementing some of the group’s suggestions, including agencywide quality standards and better coordination with state labs.

However, “recommendations for the agency to physically separate its clinical laboratories from its research laboratories, or to train researchers to uphold new quality standards, will be heavy lifts because they require continuous funding,” CBS News reported, citing an interview with Jim Pirkle, MD, PhD, Director, Division of Laboratory Sciences, National Center for Environmental Health, at the CDC.

—Stephen Beale

Related Information:

CDC’s Internal Control Weaknesses Led to Its Initial COVID-19 Test Kit Failure, but CDC Ultimately Created a Working Test Kit  

Review of the Shortcomings of CDC’s First COVID-19 Test and Recommendations for the Policies, Practices, and Systems to Mitigate Future Issues      

Collaboration to Improve Emergency Laboratory Response: Open Letter from the Association of Pathology Chairs to the Centers for Disease Control and Prevention    

The CDC Works to Overhaul Lab Operations after COVID Test Flop

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

Pathologists at Michigan Health Find Evidence That COVID-19 Survivors Who Continue to Experience Respiratory Symptoms May Have Had Lung Disease Prior to Being Exposed to the SARS-CoV-2 Coronavirus

These findings hint at the role of pre-existing conditions in raising the risk of an individual having a severe case of COVID-19 once infected

At the University of Michigan, a team of pathologists have been researching the factors that might cause some patients infected by SARS-CoV-2 to suffer persistent respiratory problems, often described as “long COVID.” They have identified factors that place some individuals at higher risk for these problems.

Little is known about how the SARS-CoV-2 coronavirus affects the body long-term. Millions of people who have survived COVID-19 infections are living with chronic symptoms, including persistent respiratory problems such as shortness of breath. However, until now, it was not clear what may be causing these symptoms in some people but not others, even after the coronavirus has completely cleared their bodies.

Now, anatomic pathologists at Michigan Medicine, formerly the University of Michigan Health, believe they may have discovered what is causing ongoing respiratory problems in some patients who have recovered from the COVID-19 infection—pre-existing conditions.

The researchers examined lung biopsies from COVID-19 patients who continued to experience lingering symptoms. They discovered in some individuals lung damage that was present prior to contracting the virus.

Jeffrey Myers, MD

“Some of the early publications and popular press around long COVID has implied or assumed that once you had COVID, everything that happens next is COVID-related,” said anatomic pathologist and senior author of the study Jeffrey Myers, MD (above), Vice Chair for Clinical Affairs and Quality at Michigan Medicine, in a news release. “Of course, that might or might not be true,” he added. (Photo copyright: University of Michigan.)

The research team analyzed lung biopsies from 18 COVID-19 survivors who were still experiencing respiratory symptoms or had abnormal computed tomography (CT) scans after the virus was no longer present in their bodies. The researchers found ground glass opacities on the radiological scans of 14 of those patients.

According to the news release, this finding indicates there were “areas of the lungs that appear as a cloudy gray color as opposed to the dark color of normal air-filled lungs, on a chest X-ray or CT scan.”

The biopsies exhibited evidence of pre-existing lung scarring and proof of diffuse alveolar damage, which is typically seen in patients with acute respiratory illnesses. Only five of the patients examined in the study were known to have lung disease prior to their COVID-19 diagnoses.

The researchers found that the most common condition present in these 18 patients was usual interstitial pneumonia (UIP). This condition, also known clinically as idiopathic pulmonary fibrosis (IPF), is a common form of pulmonary fibrosis that is characterized by progressive scarring and stiffening of both lungs.

“We were seeing a lot of UIP, which isn’t the pattern we tend to associate with acute lung injury,” said Kristine Konopka, MD, Clinical Associate Professor at Michigan Medicine and lead author of the study, in the news release. “So, we think these are patients who had lung disease prior to COVID and maybe they just weren’t being followed by primary care physicians. They then had COVID, are still sick, and their UIP is finally being picked up.”

Could Patients Have Lung Disease and Not Know it?

“The notion,” Myers noted in the news release, “that a person could have chronic lung damage and not know it was unheard of until relatively recently.” He also explained that UIP/IPF is a progressive disease that gets worse with time and that an infection like COVID-19 can accelerate the illness to a more serious condition known as an acute exacerbation of IPF, which can lead to death.

“SARS-CoV-2 comes along and does to the lung, from a pathology perspective, exactly what happens with an acute exacerbation,” Myers said.

The researchers also stated that it’s impossible to determine for certain whether the SARS-CoV-2 virus caused the UIP/IPF without the existence of full clinical histories of the patients prior to their COVID-19 diagnoses. They hope their research will motivate clinicians to be cautious before automatically attributing respiratory symptoms to long COVID in survivors of the virus. It is possible that the lung damage was present prior to the coronavirus.

“You shouldn’t make assumptions but [instead] ask the right questions, the first of which would be ‘I wonder if this is really COVID?’ What you do after that depends on the answer to that question,” he added.

The Michigan Medicine researchers published their findings in the journal eClinicalMedicine, titled, “Usual Interstitial Pneumonia Is the Most Common Finding in Surgical Lung Biopsies from Patients with Persistent Interstitial Lung Disease Following Infection with SARS-CoV-2.”

This research is an example of how pathologists can add insight and value into the deeper understanding of the processes involved in specific diseases. Dark Daily invites any of our readers who are aware of other pathologist-authored studies or published papers about COVID-19 to alert us to the availability of those works.

JP Schlingman

Related Information:

Pathologists Find Evidence of Pre-existing Chronic Lung Disease in People with Long COVID

Usual Interstitial Pneumonia is the Most Common Finding in Surgical Lung Biopsies from Patients with Persistent Interstitial Ling Disease Following Infection with SARS-CoV-2

Does the 1918 Influenza Pandemic Teach Us Anything About How and When COVID-19 Will End?

Experts weigh-in on the new Omicron variant, how pandemics conclude, and challenges ahead for clinical laboratories

Could studying how the 1918 influenza pandemic ended teach pathologists and clinical laboratory professionals how and when the current COVID-19 pandemic may end as well? And does the new Omicron variant indicate that the SARS-CoV-2 coronavirus has mutated into an endemic form of the disease?

According to the Centers for Disease Control and Prevention (CDC), the 1918 influenza (aka, the Spanish Flu) pandemic took place worldwide between 1918 and 1919. It was caused by the H1N1 virus (A/H1N1), a subtype of the Influenza A virus, and infected approximately 500 million people worldwide (a third of the human population at the time). Fifty million people died. Many were children or otherwise healthy individuals, but people from all age groups perished.

The CDC calls the Spanish Flu the “deadliest pandemic of the 20th century.” Past pandemics have generally concluded after 2.5 to 3.5 years. That’s how long it takes for new viruses to mutate and become endemic diseases, Healthline reported.

The COVID-19 pandemic has been around for about that long. It stands to reason the natural end of the COVID-19 pandemic may be just around the corner. But is it? And is the Omicron variant an indicator that the COVID-19 pandemic is winding down?

Fighting a New Coronavirus Variant

A recent McKinsey and Company report notes that, compared to the Delta variant, the new Omicron variant is:

  • 25% more infectious,
  • 25% better at evading immunity, and
  • 25% more likely to cause less severe disease.

“Our analysis suggests that in the US, this combination of characteristics would lead to Omicron replacing Delta as the dominant variant in the next few months and to a higher peak burden of disease than the country saw in the second half of 2021 (but likely below the peak reached in the winter of 2020-21),” the report states.

McKinsey analysts also acknowledged the possible impact of new therapeutics, COVID-19 vaccine booster doses, and public health measures on Omicron spread. “In the short term, an accelerated rollout of booster doses of COVID-19 vaccines is likely to be one of the best protections against an Omicron-fueled wave of the disease,” the analysts wrote.

Does How the Spanish Flu Came to an End Mirror the COVID-19 Pandemic?

Virologists and infectious disease experts explained that the Spanish Flu virus did what viruses still do: mutate and become less dangerous. Herd immunity also helped end the 1918 pandemic. 

“The 1918 influenza virus eventually mutated to the point of not having a high number of deaths—eventually over three years or so. We may very well be witnessing this process with ongoing variants of SARS-CoV-2,” virologist Rodney Rohde, PhD, Director of the Clinical Laboratory Science Program at Texas State University, told Healthline.

Todd Ellerin, MD

Today’s flu strains have “ancestral links” to the 1918 flu, and thus, the SARS-CoV-2 coronavirus will most likely also leave its mark, The Boston Herald reported. “The coronavirus will evolve and hopefully morph into a seasonal illness to which we pay little mind, but it’s still too early to tell,” Todd Ellerin, MD (above,) Director of Infectious Diseases, South Shore Health, South Weymouth, Mass., told The Boston Herald. (Photo copyright: Greg Derr/The Patriot Ledger.)

“If you think about the way viruses behave, biologically, their reason for living is to replicate and spread, and there’s really no advantage for the virus to kill the host,” infectious disease specialist Keith Armitage, MD, Professor of Medicine, Division of Infectious Diseases at Case Western Reserve University, told Healthline. “The hope is, that if the pandemic doesn’t go away, we will get new variants that are highly contagious but don’t produce much of a clinical illness,” he added.

In “2021’s Top 10 Lab Stories Confirm Important Trends,” Dark Daily’s sister publication, The Dark Report (TDR), posed a similar question in its number one story of 2021: “COVID-19: Will it Become Endemic and a Respiratory Virus that Shows Up Every Year like Influenza?”

“The question of whether SARS-CoV-2 is a pandemic that fades, as did SARS in 2003, or becomes endemic and a respiratory virus that shows up every season like influenza and the common cold, is of major concern to clinical lab administrators. That’s because clinical labs and pathology groups must continue to serve physicians and patients with the usual menu of routine, reference, and esoteric testing,” TDR noted.

Clinical Laboratories to Continue COVID Testing

It would be most helpful for medical laboratories and pathology groups to have some idea of when the pandemic will end. Unfortunately, such predictions would not be very useful.

“Since COVID-19 infections have a high number of asymptomatic transmitters, we may not fully understand how societal and environmental pressures—masks, distancing, remote working, etc.—on the virus will allow it to evolve,” Rohde told Healthline.

For now, clinical laboratories will need to continue to remain prepared as COVID-19 cases rise and people seek SARS-COV-2 tests, vaccinations, and treatments. COVID-19 testing is likely to be in demand throughout the coming year. The current surge in demand for COVID-19 tests is putting additional stress on the supply chain.

“We know pandemics end; it’s just a matter of time,” Sara Paton, PhD, Associate Professor of Epidemiology, Wright State University, told the Journal-News. “It could be in 2022, maybe later in the year, but I can’t say for sure. It could be 2023.” 

—Donna Marie Pocius

Related Information:

CDC: 1918 Pandemic

What Can We Learn from the 1918 Flu Pandemic as the Omicron Variant Spreads?

The 1918 Pandemic: A Timeline of Events

How Did the 1918 Pandemic End, and Could the Same Thing Happen with Coronavirus?

When Will the COVID-19 Pandemic End?

Will the Pandemic End in 2022?

2021 Top 10 Lab Stores Confirm Important Trends

Australian Company Launches At-Home Genetic Test in the US That Claims to Identify a Person’s ‘Risk’ for Contracting the SARS-CoV-2 Coronavirus. But What Science Supports the Test’s Ability to Accurately Assess Risk?

Since all Americans have access to free COVID-19 vaccines, many pathologists and clinical lab managers will ask if this test is even necessary. Some experts say “maybe”

Here’s another example of genetic test developers who are willing to push boundaries and sell a diagnostic test directly to consumers that has some diagnostic experts and pathologists challenging its clinical validity.

The test was developed by molecular diagnostics company Genetic Technologies Ltd. (NASDAQ:GENE) of Melbourne, Australia, and, according to an article in Science, is an at-home saliva test that “combines genetic data with someone’s age, sex, and pre-existing medical conditions to predict their risk of becoming extremely ill from COVID-19.”

In a non-peer-reviewed preprint, titled, “Development and Validation of a Clinical and Genetic Model for Predicting Risk of Severe COVID-19,” Genetic Technologies’ Chief Scientific Officer Richard Allman, PhD, and Senior Biostatistician and the study’s first author, Gillian Dite, PhD, wrote, “Using SARS-CoV-2 positive participants from the UK Biobank, we developed and validated a clinical and genetic model to predict risk of severe COVID-19. … Accurate prediction of individual risk is possible and will be important in regions where vaccines are not widely available or where people refuse or are disqualified from vaccination, especially given uncertainty about the extent of infection transmission among vaccinated people and the emergence of SARS-CoV-2 variants of concern.”

But since every American already has access to free COVID-19 vaccines, one wonders why this test would be launched in the US?

Determining Risk for COVID-19 Infection

Can a genetic test predict an individual’s risk of contracting a SARS-CoV-2 infection that would require hospitalization or cause death? Genetic Technologies and its US partner, Infinity BiologiX (IBX) of Piscataway, N.J., believe so.

According to a Genetic Technologies news release, the saliva test, which reportedly costs $175, enables a “leading-edge risk assessment that estimates your personal risk of severe disease,” IBX says on its website.

The at-home saliva-based test, which is intended for people age 18 and older, gives a risk score for contracting a serious COVID-19 case based on genetic and clinical information, IBX stated in its own news release.

The two companies partnered with Vault Health, a “virtual platform for telemedicine and diagnostics” developer, to distribute, and sell the COVID-19 Serious Disease Risk Test in the US.

Genetic Technologies’ COVID-19 Risk Test

In the IBX news release, IBX’s Chief Executive Officer, Robin Grimwood, said, “We see this initial agreement for the sale and distribution of Genetic Technologies’ COVID-19 Risk Test (above) as a critical collaboration in line with our mission to understand the genetic causes of common, complex diseases and to discover diagnoses, treatments and, eventually, cures for these diseases.” However, as Dark Daily’s sister publication The Dark Report previously reported, some geneticists, epidemiologists, and clinical laboratory professionals have expressed concerns. (Photo copyright: Infinity BiologiX.)

Is There a Place for Genetic COVID-19 Risk Test in the US?

“Alongside existing treatment options and vaccines, we believe this test will enable more insightful decisions for states, workplaces, and individuals,” said Simon Morriss, Genetic Technologies’ CEO, in the news release.

Meanwhile, some experts are uncertain about predictive types of testing for the SARS-CoV-2 coronavirus. “I think it’s premature to use a genetic test to predict a person’s likely COVID-19 severity. We don’t understand exactly what these genetic variants mean or how they affect disease,” epidemiologist Priya Duggal PhD, a professor in the Genetics Epidemiology Division at the Johns Hopkins University School of Public Health, told Science.

Launched without FDA Clearance?

A recent Intelligence Briefing from Dark Daily’s sister publication The Dark Report, noted that the companies introduced the test in the US without a US Food and Drug Administration (FDA) review.

According to Science, “The test debuts in a regulatory gray zone …. The two companies did not seek [FDA] approval for validity because, [Genetic Technologies Chief Scientific Officer Richard Allman] says, the test is not a direct-to-consumer product that falls under its review. After a customer receives results from IBX’s federally-approved labs, they can consult with a ‘telehealth’ physician.”

“We are uniquely and strategically positioned with our partners to deliver the test and provide remote telehealth services and reporting, utilizing our extensive array capability and capacity across a number of platforms,” Grimwood said in the IBX news release.

However, Science reported that “Several geneticists who reviewed the company’s preprint” said “the test needs to be validated in other, more diverse populations than one detailed in the UK Biobank, and they wonder whether its predictions are reliable for people infected with new SARS-CoV-2 variants.”

“It’s a good start, but by no means is it calibrated or validated sufficiently to say this is a test I would take, or my wife should take,” cancer geneticist Stephen Chanock, MD, Director of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, National Institutes of Health, told Science.

The question remains unanswered as to why a genetic risk test for SARS-CoV-2 and its variants is needed in the United States. Nevertheless, clinical laboratory leaders and pathologists may want to monitor these developments for new biomarkers and COVID-19 diagnostics.

—Donna Marie Pocius

Related Information

Test Improves COVID-19 Prevention and Management Capabilities for Employers, Governments, and Public Health Decision Makers; Gene’s COVID-19 Risk Test Released for Sale in the US

Infinity BiologiX, Genetic Technologies, and Vault Health Launch New Test to Assess Severity of COVID-19 in Individuals

Intelligence Briefing: The Dark Report

Would You Have Your DNA Tested to Predict How Hard COVID-19 Would Strike? Should You?

Development and Validation of a Clinical and Genetic Model for Predicting Risk of Severe COVID-19

Mapping the Human Genetic Architecture of COVID-19 Using Worldwide Meta-Analysis

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