Quest said a ‘technical issue’ had delayed reporting of test data to the state and claimed that patients and providers still received the results in a timely manner
Florida Governor Ron DeSantis has ordered state agencies to cut ties with Quest Diagnostics due to delays in reporting nearly 75,000 COVID-19 clinical laboratory test results going back as far as April. The medical laboratory giant provided the backlogged data in what the state described as an “unacceptable dump” that inflated the state’s case count and SARS-CoV-2 test positivity rate reported for August 31.
“The law requires all COVID-19 results to be reported to DOH in a timely manner,” DeSantis said in a statement following the announcement of his directives. “To drop this much unusable and stale data is irresponsible. I believe that Quest has abdicated their ability to perform a testing function in Florida that the people can be confident in. As such I am directing all executive agencies to sever their COVID-19 testing relationships with Quest effective immediately.”
DeSantis later elaborated during a Sept. 1 press conference. “These labs know that their results are being used by people to determine the course of certain policies,” he said. “Someone will say the positive rate has gone up. Maybe we can’t go [to] in-person schooling.”
Florida Governor Ron DeSantis (above) answers questions from reporters concerning COVID-19 reporting. Click here to watch a video of the press briefing. (Video copyright: Miami Herald.)
Quest Diagnostics Said, ‘Technical Issue’ Caused Delay in Reporting
In a statement that described the delay as a “technical issue” involving a subset of the approximately 1.4 million test results reported to the State of Florida, Quest said the issue has been resolved and that it “did not affect or delay reporting of test results to providers and patients.”
Still, “Quest Diagnostics takes seriously our responsibility to report laboratory data to public health authorities in a timely manner to aid pandemic response,” the company said. “We apologize for this matter and regret the challenge it poses for public health authorities in Florida.”
The company added that it “has provided more COVID-19 testing on behalf of the citizens of Florida than any other laboratory and we believe we are well positioned to continue to effectively aid patient care and public health response for the state. We remain open to working with the state Department of Health to provide testing that meets the needs required for patient care and public health response.”
A Quest spokesperson told WTLV-TV in Jacksonville that the glitch was related to missing contact information for some of the tested patients. The missing data “was maintained in a separate system outside our typical data reporting process to the state,” she said. “When we became aware that we had not reported the [COVID-19 test] data—once the missing information was completed—to state public health [officials], we promptly informed the appropriate state authorities of the delayed reporting, provided the information on the specimens, and remedied our procedure.”
Impact of Reporting Delay on State
Most of the delayed results of the COVID-19 tests were more than two weeks old, and some were almost five months old, the DOH said. The Tampa Bay Times reported that most were from mid-June to mid-July, “when Florida was reporting record-high cases.”
Without the backlogged data, the state would have reported 3,773 new cases on August 31, the DOH said, but the delayed results added 3,870 cases, bringing the total to 7,643. The backlogged data also inflated the reported positivity rate from 5.9% to 6.8%, the DOH said. The positivity rate is regarded as a key indicator of the degree of disease transmission in a community, Johns Hopkins Bloomberg School of Public Health noted.
Impact on Quest Diagnostics
Most of Quest’s COVID-19 testing in Florida has been conducted at private sites, the Tallahassee Democrat reported. However, in May, June, and July, the Florida Division of Emergency Management announced a series of partnerships with Quest Diagnostics to provide walk-up and drive-in testing services at local retailers, including Publix and The Home Depot (NYSE:HD).
“Quest Diagnostics was only being utilized at a limited number of state-supported sites,” FDEM spokesman Jason Mahon told the Tallahassee Democrat, adding that the state should be able to find other clinical laboratory companies to replace that work.
However, even if Quest’s testing for the state was limited, the governor’s order could still be costly to the company. A search of the Florida Accountability Contract Tracking System database indicates that the state paid Quest nearly $1.8 million for COVID-19 testing services. And the state has used Quest to provide non-COVID-19 services amounting to $7.9 million in 2019 and 2020 as well, according to the database. It’s not clear how the latter will be affected by Governor DeSantis’ directives.
Overall, Quest accounts for at least 13% of the six million COVID-19 tests run in the Florida, the Tampa Bay Times reported, citing data from the DOH.
Other Times Florida Had Issues with Clinical Laboratory Companies
Quest is not the first clinical laboratory company to run afoul of Florida regulatory agencies. On August 12, the DOH announced that Niznik Lab Corp. of Miami submitted a backlog of 4,000 cases dating back to June 23, CBSNews reported.
“This backlog severely skews today’s daily report for Miami-Dade County and is not reflective of current trends,” the agency stated in a press release.
And this isn’t the first time that Florida has had issues with COVID-19 testing contracts, as Dark Dailypreviously reported.
On May 15, the state cancelled a contract with MicroGen Diagnostics to provide testing services, due to concerns about reliability and processing speed, Florida Bulldog reported. AdventHealth, a large non-profit health system in Altamonte Springs, Fla., cited similar issues in cancelling a contract with MicroGen Diagnostics, according to USA Today.
According to Florida Bulldog, “Gov. Ron DeSantis touted an $11-million COVID-19 testing deal with a Texas-based lab now embroiled in controversy and facing questions about the reliability of its tests,” and that, “under pressure” the Governor in an April 22 press conference said, “we have two contracts in place with two new labs that will increase our lab capacity by 18,000 samples per day.”
Florida Bulldog went on to state, “One of those firms was Southwest Regional PCR, of Lubbock, Texas, which does business as MicroGenDX, headquartered in Orlando. The Executive Office of the Governor had signed an $11-million contract the day before with the firm for ‘COVID-19 Diagnostic Testing ($99 per test 8,000 tests per day for 14 days).’
“Less than a month later, however, the governor’s office quietly canceled the contract amid questions about MicroGenDX’s dependability,” Florida Bulldog reported.
In addition, an $11.3 million state contract with Indur Services was reduced to $2.2 million for testing supplies after media outlets reported that the company’s founder had pleaded guilty to multiple federal insurance fraud charges in Texas, Florida Bulldog reported.
All levels of government in the United States are under extreme pressure to respond to the COVID-19 pandemic in an effective and timely manner. The results of clinical laboratory tests for SARS-CoV-2 are the closely-watched measure of whether infections are increasing, holding steady, or decreasing in a community, a region, or a state.
That is why any delay in reporting the tests results to government entities is a cause for concern. It is also why the news media are quick to report any problems clinical laboratories have with their COVID-19 testing programs.
Abbott sends the SARS-CoV-2 test results directly to patients’ smartphones, which can be displayed to gain entrance into areas requiring proof of COVID-19 testing
There is no greater example that COVID-19 is a major force for change in the clinical laboratory industry than the fact that—though the US federal government pays 50% of the nation’s total annual healthcare spend of $3.5 trillion—it recently spent $760 million to purchase 150 million COVID-19 tests from Abbott Laboratories (NYSE:ABT), an American multinational medical devices and healthcare company headquartered in Abbott Park, Ill., “to expand strategic, evidence-based testing in the United States,” according to the company’s website.
In August, the federal Food and Drug Administration (FDA) granted an emergency use authorization (EUA) to Abbott for its BinaxNOW portable rapid-response COVID-19 antigen (Ag) test. The credit-card sized test costs $5 and can return clinical laboratory test results in minutes, rather than hours, days, or in some cases, weeks, the Wall Street Journal (WSJ) reported.
The test includes a free smartphone app called NAVICA, which enables those tested to receive their test results directly on their mobile devices—bypassing the patient’s primary care physicians.
According to Abbott’s website, the app “allows people who test negative to get an encrypted temporary digital NAVICA Pass, similar to an airline boarding pass. NAVICA-enabled organizations will be able to verify an individual’s negative COVID-19 test results by scanning the individual’s digital NAVICA Pass to facilitate entry into facilities.”
This feature of Abbott’s new COVID-19 test is a good example of how quickly innovation in the medical laboratory testing profession is bringing new features and new capabilities to the marketplace. By marrying the SARS-CoV-2 test with the NAVICA Pass feature, Abbott hopes to deliver increased value—not just to physicians and their patients—but also to employers with employee screening programs and federal government programs designed to screen federal employees, as well as being used for screening travelers at airports and other transportation hubs.
Abbott appears to be banking that in the future such identification will be required to “enter organizations and other places where people gather,” as the company’s website states.
Testing Limited to CLIA-Certified Clinical Laboratories
An HHS news release announcing the government’s planned distribution of the BinaxNOW tests stated that “Testing will be potentially deployed to schools and to assist with serving other special needs populations.”
In the news release, Alex Azar, HHS Secretary, said, “By strategically distributing 150 million of these tests to where they’re needed most, we can track the virus like never before and protect millions of Americans at risk in especially vulnerable situations.”
The EUA adds that “Testing of nasal swab specimens using [BinaxNOW] … is limited to laboratories certified under CLIA that meet the requirements to perform high, moderate, or waived complexity tests. This test is authorized for use at the [point of care], i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation.”
The FDA’s EUA describes the BinaxNOW portable rapid-response COVID-19 antigen test (above) as “a lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein antigen from SARS-CoV-2 in direct nasal swabs from individuals suspected of COVID-19 by their healthcare provider within the first seven days of symptom onset.” The test costs $5 and Abbott sends results directly to the patient’s smartphone using the free NAVICA app included with the test. (Photo copyright: Abbott Laboratories.)
IVD Companies See Boom in COVID-19 Test Sales
Demand for COVID-19 testing has created opportunities for in vitro diagnostics (IVD) companies that can develop and bring tests to market quickly.
Recent issues of Dark Daily’s sister print publication—The Dark Report (TDR)—covered IVD companies’ second quarter (Q2) boom in sales of COVID-19 instruments and tests, while also noting a fall-off in routine clinical laboratory testing during the COVID-19 pandemic.
Abbott Laboratories saw molecular diagnostics sales increase 241% in Q2 driven by $283 million in sales of COVID-19 testing, while rapid diagnostic COVID-19 testing rose 11% on $180 million in sales in Q2, TDR reported, based on Abbott data.
“There is huge economic incentive for diagnostic companies to develop technologies that can be used to create rapid tests that are cheap to perform,” said Robert Michel, Publisher and Editor-in-Chief of TDR and Dark Daily. “In this sense, COVID is a major force for change.”
“This new COVID-19 antigen test is an important addition to available tests because the results can be read in minutes, right off the testing card,” said Jeff Shuren, MD, JD (above), Director of the FDA’s Center for Devices and Radiological Health (CDRH), in an FDA news release announcing the federal government’s $760 million purchase of 150 million Abbott BinaxNOW rapid-response antigen COVID-19 tests. “This means people will know if they have the virus in almost real-time. Due to its simpler design and the large number of tests the company anticipates making in the coming months, this new antigen test is an important advancement in our fight against the pandemic.” (Photo copyright: The New York Times.)
Thus, Abbott is determined to ensure this product launch is successful and that the test works as promised. According to a news release, “In data submitted to the FDA from a clinical study conducted by Abbott with several leading US research universities, the BinaxNOW COVID-19 Ag Card demonstrated sensitivity of 97.1% (positive percent agreement) and specificity of 98.5% (negative percent agreement) in patients suspected of COVID-19 by their healthcare provider within the first seven days of symptom onset.”
“The massive scale of this test and app will allow tens of millions of people to have access to rapid and reliable testing,” said Joseph Petrosino, PhD, professor and chairman, Molecular Virology and Microbiology, Baylor College of Medicine, in the Abbott news release. “With lab-based tests, you get excellent sensitivity but might have to wait days or longer to get the results. With a rapid antigen test, you get a result right away, getting infectious people off the streets and into quarantine so they don’t spread the virus.”
Abbott has invested hundreds of millions of dollars in two manufacturing facilities where the tests will be made, John Hackett Jr, PhD, an immunologist and Abbott’s Divisional Vice President Applied Research and Technology, and lead scientist on the BinaxNOW project, told The Atlantic.
“Our nation’s frontline healthcare workers and clinical laboratory personnel have been under siege since the onset of this pandemic,” said Charles Chiu, MD, PhD, professor of Laboratory Medicine at University of California, San Francisco, in the Abbott news release. “The availability of rapid testing for COVID-19 will help support overburdened laboratories, accelerate turnaround times, and greatly expand access to people who need it.”
However, other experts are not so sure. In the Atlantic article, Michael Mina MD, PhD, Assistant Professor Epidemiology at Harvard’s T.H. Chan School of Public Health, voiced the need to test both asymptomatic and pre-symptomatic people. “This is the type of [COVID-19] test we have been waiting for—but may not be the test.”
Nevertheless, the federal government’s investment is significant. Abbott plans to start shipping tens of millions of tests in September and produce 50 million tests per month starting in October, Forbes reported.
Shifting Clinical Laboratory Paradigms
BinaxNOW will be performed without doctors’ orders, in a variety of locations, and results go directly to patients’ smartphone—without a pathologist’s interpretation and medical laboratory report. This is new ground and the impact on non-CLIA labs, and on healthcare in general, is yet to be seen.
Clinical laboratory managers will want to monitor the rise of rapid-response tests that can be easily accessed, conducted, and reported on without physician input.
Clinical laboratories involved in genetic testing may find this welcomed news, after a pair of studies conducted in 2019 raised concerns about CRISPR base editing. The researchers of those studies observed that it “causes a high number of unpredictable mutations in mouse embryos and rice,” Chemical and Engineering News (C&EN) reported, adding, “Other groups have raised concerns about off-target mutations caused when the traditional CRISPR-Cas9 form of gene editing cuts DNA at a location that it wasn’t supposed to touch. The results of the new studies are surprising, however, because scientists have lauded base editors as one of the most precise forms of gene editing yet.”
Nevertheless, UC Berkeley’s latest breakthrough is expected to drive development of new and more accurate CRISPR-Cas genome-editing tools, which consist of base editors as well as nucleases, transposases, recombinases, and prime editors.
Understanding CRISPR Base Editors At a ‘Deeper Level’
Harvard University Chemistry and Chemical Biology Professor David Liu, PhD, who co-authored the study, explained the significance of this latest discovery.
“While base editors are now widely used to introduce precise changes in organisms ranging from bacteria to plants to primates, no one has previously observed the three-dimensional molecular structure of a base editor,” he said in a UC Berkeley news release. “This collaborative project reveals the beautiful molecular structure of a state-of-the-art highly-active base editor—ABE8e—caught in the act of engaging a target DNA site.”
UC Berkeley Professor Jennifer Doudna, PhD (above), who served as senior author of the study, says scientists may now have the information necessary to refine base editors and improve their precision and genome-targeting ability. “This structure helps us understand base editors at a much deeper level,” she said in the UC Berkeley statement. “Now that we can see what we’re working with, we can develop informed strategies to improve the system.” (Photo copyright: UC Berkeley.)
Jennifer Doudna, PhD, UC Berkeley Professor, Howard Hughes Medical Institute Investigator, and senior author of the study, has been a leading figure in the development of CRISPR-Cas9 gene editing. In 2012, Doudna and Emmanuelle Charpentier, PhD, Founding, Scientific and Managing Director at Max Planck Unit for the Science of Pathogens in Berlin, led a team of researchers who “determined how a bacterial immune system known as CRISPR-Cas9 is able to cut DNA, and then engineered CRISPR-Cas9 to be used as a powerful gene editing technology.” In a 2017 news release, UC Berkeley noted that the work has been described as the “scientific breakthrough of the century.”
Viewing the Base Editor’s 3D Shape
CRISPR-Cas9 gene editing allows scientists to permanently edit the genetic information of any organism, including human cells, and has been used in agriculture as well as medicine. A base editor is a tool that manipulates a gene by binding to DNA and replacing one nucleotide with another.
According to the recent UC Berkeley news release, the research team used a “high-powered imaging technique called cryo-electron microscopy” to reveal the base editor’s 3D shape.
Genetic Engineering and Biotechnology News notes that, “The high-resolution structure is of ABE8e bound to DNA, in which the target adenine is replaced with an analog designed to trap the catalytic conformation. The structure, together with kinetic data comparing ABE8e to earlier ABEs [adenine base editors], explains how ABE8e edits DNA bases and could inform future base-editor design.”
The graphic above, taken from the UC Berkeley news release, shows the “3D structure of a base editor, comprised of the Cas9 protein (white and gray), which binds to a DNA target (teal and blue helix) complementary to the RNA guide (purple), and the deaminase proteins (red and pink), which switch out one nucleotide for another.” (Image and caption copyright: UC Berkeley.)
Knowing the Cas9 fusion protein’s 3D structure may help eliminate unintended off-target effects on RNA, extending beyond the targeted DNA. However, until now, scientists have been hampered by their inability to understand the base editor’s structure.
“If you really want to design truly specific fusion protein, you have to find a way to make the catalytic domain more a part of Cas9, so that it would sense when Cas9 is on the correct target and only then get activated, instead of being active all the time,” study co-first author Audrone Lapinaite, PhD, said in the news release. At the time of the study, Lapinaite was a postdoctoral fellow at UC Berkeley. She is now an assistant professor at Arizona State University.
“As a structural biologist, I really want to look at a molecule and think about ways to rationally improve it. This structure and accompanying biochemistry really give us that power,” added UC Berkeley postdoctoral fellow Gavin Knott, PhD, another study co-author. “We can now make rational predications for how this system will behave in a cell, because we can see it and predict how it’s going to break or predict ways to make it better.”
Clinical laboratory leaders and pathologists will want to monitor these new advances in CRISPR technology. Each breakthrough has the power to fuel development of cost-effective, rapid point-of-care diagnostics.
The KCL researchers’ new models for predicting which patients will need hospitalization and breathing support may be useful for pathologists and clinical laboratory scientists
One more window into understanding the SARS-CoV-2 coronavirus may have just opened. A British study identified six distinct “clusters” of symptoms that the research scientists believe may help predict which patients diagnosed with COVID-19 will require hospitalization and respiratory support. If further research confirms these early findings, pathologists and medical laboratory managers may gain new tools to diagnose infections faster and more accurately.
Launched in March in the United Kingdom and extended to the United States and Sweden, the app has attracted more than four million users who track their health and potential COVID symptoms on a daily basis.
Increased Accuracy in Predicting COVID-19 Hospitalizations
KCL researchers identified six distinct “types” of COVID-19, each distinguished by a particular cluster of symptoms. They include headaches, muscle pains, fatigue, diarrhea, confusion, loss of appetite, shortness of breath, and more. The researchers also found that COVID-19 disease progression and outcome also vary significantly between people, ranging from mild flu-like symptoms or a simple rash to severe or fatal conditions.
Using app data logged by 1,600 users in March and April, the researchers developed an algorithm that combined information on age, gender, body mass index (BMI), and pre-existing conditions with recorded symptoms from the onset of the illness through the first five days. The researchers then tested the algorithm using a second independent dataset of 1,000 users, logged in May.
In a news release, the KCL researchers identified the six clusters of symptoms as:
Flu-like with No Fever: Headache, loss of smell, muscle pains, cough, sore throat, chest pain, no fever.
Flu-like with Fever: Headache, loss of smell, cough, sore throat, hoarseness, fever, loss of appetite.
Gastrointestinal: Headache, loss of smell, loss of appetite, diarrhea, sore throat, chest pain, no cough.
Severe Level One, Fatigue: Headache, loss of smell, cough, fever, hoarseness, chest pain, fatigue.
Severe Level Two, Confusion: Headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, confusion, muscle pain.
Severe Level Three, Abdominal and Respiratory: Headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, confusion, muscle pain, shortness of breath, diarrhea, abdominal pain.
Using the data, the researchers were able to more accurately predict—78.8% versus 69.5%—which of the six symptom clusters placed patients at higher risk of requiring hospitalization and breathing support (ventilation or additional oxygen) than with prediction models based on personal characteristics alone. For example, nearly 50% of the patients in cluster six (Severe Level Three, Abdominal and Respiratory) ended up in the hospital, compared with 16% of those in cluster one (Flu-like with No Fever).
“These findings have important implications for care and monitoring of people who are most vulnerable to severe COVID-19,” Claire Steves, MD, PhD (above left), Clinical Senior Lecturer at King’s College London, said in the KCL news release. “If you can predict who these people are at day five, you have time to give them support and early interventions, such as monitoring blood oxygen and sugar levels, and ensuring they are properly hydrated—simple care that could be given at home, preventing hospitalizations and saving lives.” (Photo copyright: King’s College London.)
According to the Zoe website, the ongoing research is led by:
Prof. Tim Spector, FMedSci, Professor of Genetic Epidemiology at King’s College London and Director of TwinsUK, an adult registry of twins in the United Kingdom;
Andrew Chan, MD, Professor of Medicine at Harvard Medical School, Professor of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health and Chief of the Clinical and Translational Epidemiology Unit, CTEU Massachusetts General Hospital; and
Encouraging Everyone to Use the COVID-Symptom Study App
The study points out that—broadly speaking—people with cluster four, five, or six COVID-19 symptoms tended to be older and frailer and were more likely to be overweight and have pre-existing conditions, such as diabetes or lung disease, than those with cluster one, two, or three symptoms.
“Our study illustrates the importance of monitoring symptoms over time to make our predictions about individual risk and outcomes more sophisticated and accurate,” said lead researcher Carole Sudre, PhD (above), a Research Fellow at King’s College London and the study’s lead researcher, in the KCL news release. “This approach is helping us to understand the unfolding story of this disease in each patient so they can get the best care.” (Photo copyright: University College London.)
Tim Spector, FMedSci, Head of the Department of Twin Research and Genetic Epidemiology, and Professor of Genetic Epidemiology at King’s College London, encourages everyone to download the COVID Symptom Study app and help increase the data available to researchers.
“Data is our most powerful tool in the fight against COVID-19,” Spector said in the KCL news release. “We urge everyone to get in the habit of using the app daily to log their health over the coming months, helping us to stay ahead of any local hotspots or a second wave of infections.”
As the body of knowledge surrounding COVID-19 grows, clinical laboratory professionals would be well advised to remain informed on further research regarding not only the potential for COVID-19 variants to exist, but also the evolving guidance on infection prevention and testing.
Pooled testing could become a critical tool for clinical laboratories to spot the SARS-CoV-2 coronavirus among asymptomatic and pre-symptomatic individuals
COVID-19 testing for individuals has expanded in the US, but the number of people actually tested remains a small proportion of the country’s total population and clinical laboratory testing supply shortages continue to hamper progress. A technique known as pooled testing may help. Federal experts hope it will substantially increase the number of individuals who are tested for the SARS-CoV-2 coronavirus before it makes a possible resurgence in the fall.
One-by-one, some of the nation’s largest clinical laboratory organizations are developing the capability to do pooled testing. For example, on July 18, the Food and Drug Administration (FDA) announced it had issued Quest Diagnostics (NYSE:DGX) an Emergency Use Authorization (EUA) for its SARS-CoV-2 rRT-PCR test, and that it is valid for up to four individual samples as a pooled test.
Quest’s rRT-PCR test was the first COVID-19 diagnostic test to be authorized for use with pooled samples, the FDA noted in a new release.
In the FDA’s statement announcing Quest’s EUA for its rRT-PCR test, Stephen M. Hahn, MD (above), FDA Commissioner, said, “This EUA for sample pooling is an important step forward in getting more COVID-19 tests to more Americans more quickly while preserving testing supplies.” He added, “Sample pooling becomes especially important as infection rates decline and we begin testing larger portions of the population.” (Photo copyright: CBS News.)
Following the announcement of Quest’s EUA, on July 24 the FDA announced LabCorp’s (NYSE:LH) EUA for its COVID-19 real-time reverse transcription polymerase chain reaction (rRT-PCR) test. The test, the EUA states, is intended for the “qualitative detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens” in individuals suspected of COVID-19, using “a matrix pooling strategy (i.e., group pooling strategy), containing up to five individual upper respiratory swab specimens (nasopharyngeal, mid-turbinate, anterior nares or oropharyngeal swabs) per pool and 25 specimens per matrix.”
Exponentially Increasing Testing
In pooled testing, instead of performing a coronavirus test on every specimen received by a clinical laboratory, samples from each individual specimen are taken and then combined with samples from other specimens. A single test is then performed on the entire collection of specimen samples.
If the results of the pooled samples are negative for coronavirus, it is safe to assume that all the specimens in the batch are negative for the virus. If the pooled sample comes back positive, then it will be necessary to go back to the original specimens in that pooled sample and test each specimen individually.
In an exclusive interview with Dark Daily’s sister print publication The Dark Report, Steven H. Hinrichs, MD, Chair of the Department of Pathology and Microbiology at the University of Nebraska Medical Center (UNMC), noted that one pitfall of pooled testing is that it works best in areas of low virus prevalence.
“For pooled testing, the ideal level of low prevalence would be an infection rate below 10%,” he said, adding, “For COVID-19 test manufacturers, pooled testing has the potential to reduce the number of standard tests labs run by roughly 40% to 60%, depending on the population being tested.
“Cutting the number of COVID-19 tests would be a disadvantage for test manufacturers, because pooled tests would identify large numbers of uninfected individuals who would not require standard testing with EUA tests.
“On the other hand, this policy would be a significant advantage for US labs because pooled testing would cut the number of standard tests,” he continued. “Clinical labs would save money on tests, reagents, and other supplies. It would also ease the burden on the lab’s technical staff,” Hinrichs concluded.
“In our study, we show that it’s reasonable to pool five samples, although we realized that some people may want to pool 10 samples at once,” noted Hinrichs. “But even if one sample is positive in a pool of five, then testing five samples at once saves 80% of our costs if all of those samples are negative. But, if one sample is positive, each of those five samples needs to be retested using the standard test,” Hinrichs explained.
During an American Society for Microbiology (ASM) virtual conference, Deborah Birx, MD, White House Coronavirus Response Coordinator, said, “Pooling would give us the capacity to go from a half a million tests per day to potentially five million individuals tested per day,” STAT reported.
Advantages of using pooled testing for the coronavirus include:
Expanding the number of individuals tested,
Stretching laboratory supplies, and
Reducing the costs associated with testing.
Health officials believe that individuals who have COVID-19 and are asymptomatic are largely responsible for the rising number of coronavirus cases in the US, STAT reported.
“It allows you to test more frequently in a population that may have a low prevalence of disease,” Benjamin Pinsky, MD, PhD, Associate Professor, Departments of Pathology and Medicine at Stanford University School of Medicine, told STAT. “That would allow you to test a lot of negatives, but also identify individuals who are then infected, before they develop symptoms.”
Pooled testing also could be advantageous for communities where COVID-19 is not prevalent, in neighborhoods that need to be tested during an outbreak, and for schools, universities, organizations, and businesses that want to remain safely open while periodically monitoring individuals for the virus, CNN reported.
“The goal is to increase the capacity of testing in a relatively straightforward fashion,” Pinsky told STAT. “The caveat is that by pooling the sample, you’re going to reduce the sensitivity of the test.”
According to Pinsky, “pooling only makes sense in places with low rates of COVID-19, where you expect the large majority of tests to be negative. Otherwise, too many of the pools would come back positive for it to work as a useful surveillance tool,” STAT reported.
As Clinical Lab Testing Increases, Pooled Testing for COVID-19 Could Be Critical
Pooled testing has been used in other countries, including China, to test larger amounts of people for COVID-19.
“If you look around the globe, the way people are doing a million tests or 10 million tests is they’re doing pooling,” Birx said during the ASM virtual conference, CNN reported.
In a press release, the American Clinical Laboratory Association (ACLA) stated that about 300,000 tests for COVID-19 were performed per day in labs across the US in late June. That number was up from approximately 100,000 tests being performed daily in early April.
“All across the country, clinical laboratories are increasing the number of labs processing tests, purchasing additional testing platforms, and expanding the number of suppliers to provide critical testing materials,” said Julie Khani, ACLA President in the press release. “However, the reality of this ongoing global pandemic is that testing supplies are limited. Every country across the globe is in need of essential testing supplies, like pipettes and reagents, and that demand is likely to increase in the coming months.”
Clinical laboratory managers will want to keep an eye on these developments. As the need for COVID-19 testing increases, pooled testing may provide an efficient, cost-effective way to spot the coronavirus, especially among those who are asymptomatic or pre-symptomatic and who display no symptoms.
Pooled testing could become a critical tool in the diagnosis of COVID-19 and potentially decrease the overall number of deaths.
Ability to produce unbroken DNA sequencing could eventually be used by medical laboratories to identify gene sequences that play significant roles in a variety of diseases and health conditions
While near 24/7 coronavirus coverage occupies much of the media, it is refreshing to report on important breakthroughs in clinical laboratory medicine and diagnostics that are unrelated to the COVID-19 pandemic. It wasn’t long ago that the top stories in advanced medicine revolved around whole-genome sequencing, so it’s nice to return to the topic, if just for a little while.
Using nanopore sequencing technology from multiple companies, researchers at the University of California Santa Cruz Genomics Institute (UCSC Genomics Institute) have produced what they say is the first telomere-to-telomere or end-to-end map of the human X chromosome. This could prove to be a major milestone for genomics research and help scientists gain a better understanding of certain genetic conditions.
The completely gapless DNA sequencing was produced by using new sequencing technologies that enable much longer reads of strings of DNA base pairs. In the past, most sequencing technologies produced relatively short reads of each sequence, which then had to be painstakingly pieced together to assemble the complete genome.
“With nanopore sequencing we get ultra-long reads of hundreds of thousands of base pairs that can span an entire repeat region, so that bypasses some of the challenges,” said Karen Miga, PhD, a post-doctoral research scientist at the UCSC Genomics Institute and lead author of the study, in a UCSC news release.
UCSC Researchers Find ‘Rich’ Information in the ‘Gaps’ in Reference Sequences
Nanopore sequencing technology from Oxford Nanopore Technologies was combined with sequencing technologies from Pacific Biosciences (PacBio) and Illumina, as well as with optical maps from Bionano, to produce the results of the research. The combination of these technologies allowed the UCSC team to produce a whole-genome sequence assembly with no gaps and with a previously unforeseen level of accuracy.
“These repeat-rich sequences were once deemed intractable, but now we’ve made leaps and bounds in sequencing technology,” Miga said.
According to the Oxford Nanopore Technologies website, “Nanopore sequencing is a unique, scalable technology that enables direct, real-time analysis of long DNA or RNA fragments. It works by monitoring changes to an electrical current as nucleic acids are passed through a protein nanopore. The resulting signal is decoded to provide the specific DNA or RNA sequence.”
By filling in gaps in the human genome, the UCSC researchers opened up new possibilities to finding clues and answers regarding important questions about our genes and how they may contribute to illnesses.
“We’re starting to find that some of these regions where there were gaps in the reference sequence are actually among the richest for variation in human populations, so we’ve been missing a lot of information that could be important to understanding human biology and disease,” said Karen Miga, PhD (above), post-doctoral researcher at the UCSC Genomics Institute and lead author of the study, in the UCSC news release. (Photo copyright: UCSC Genomics Institute.)
During their research, the team had to manually resolve several gaps in the sequence and identify variants within the repeat sequence to serve as markers. They were then able to align the long reads and connect them together to span the centromere of the X chromosome. The centromere is a difficult region of repetitive DNA that is found in every chromosome. It encompasses an area of very repetitive DNA that spans 3.1 million base pairs.
“For me, the idea that we can put together a 3-megabase-size [3-million base pairs] tandem repeat is just mind-blowing. We can now reach these repeat regions covering millions of bases that were previously thought intractable,” Miga said.
The researchers also had to employ a polishing strategy using data obtained from different sequencing technologies to ensure accuracy.
“We used an iterative process over three different sequencing platforms to polish the sequence and reach a high level of accuracy,” Miga explained. “The unique markers provide an anchoring system for the ultra-long reads, and once you anchor the reads, you can use multiple data sets to call each base.”
Linking Gene Variations to Specific Genetic Diseases
Besides the advantages of providing ultra-long reads, nanopore sequencing can also detect bases that have been modified by methylation, a biological process by which methyl groups are added to the DNA molecule. Methylation is an epigenetic change that can alter the activity of a DNA segment without changing the sequence, and can have important effects on the DNA structure and gene expression. When located in a gene promoter, DNA methylation typically acts to repress gene transcription.
The researchers were able to observe and map patterns of methylation on the X chromosome and found some interesting trends in methylation patterns within the centromere. By looking at this previously unmapped area of the genome, scientists may be able to search for potential links between these variations and genetic diseases.
“You could be turning a blind eye to some of the richest sequence diversity that exists in the human population, and some of that sequence diversity that you’re not looking at could be correlated with disease in a way we’ve never been able to study before,” Miga told OneZero.
The work performed by researchers at the UCSC Genomics Institute could provide genetic scientists with a road map for producing complete sequences in other human chromosomes. This may lead genomic researchers to identify gene sequences that play significant roles in a variety of diseases and health conditions. In turn, this would give clinical laboratories new biomarkers for diagnosing disease and other chronic conditions in patients.
