What’s New with COVID-19 diagnostic testing from IVD market research firm Kalorama
FDA Tightens on Variants
The U.S. Food and Drug Administration (FDA) has released new guidance for developers of products for COVID-19 diagnostics, vaccines, and treatments, with a particular emphasis on addressing coronavirus variants.
The guidance follows a safety alert from the agency in January warning of the risk for false-negative results on coronavirus tests due to variants.
The FDA also issued an updated version of its previously released emergency use authorization for vaccines to prevent COVID-19 guidance document. This document provides advice on modifying vaccines to ensure effectiveness against variants through clinical immunogenicity studies. It’s possible that in the future, clinical studies may not need to be submitted to support use of modified versions of authorized vaccines, according to the agency.
Other guidance addresses therapeutics for the coronavirus, such as development of monoclonal antibody products targeting SARS-CoV-2, including addressing the effect of emerging variants during the COVID-19 public health emergency.
Thermo Launches 8,000 Sample COVID-19/Day Test
Thermo Fisher Scientific, the world leader in serving science, today launched its CE-IVD-Marked, Applied Biosystems TaqPath COVID‑19 HT Kit that is compatible with the Amplitude platform. The high-throughput solution enables clinical and public health laboratories to efficiently test up to 8,000 COVID-19 samples a day with fewer staffing requirements and a reliable supply of kits, reagents and consumables.
The highly automated Amplitude platform is a molecular diagnostic system that allows labs to increase their COVID-19 testing capacity by combining Thermo Fisher’s extraction and real-time PCR instruments with liquid handling products from Tecan Group. The system leverages a high-throughput version of Thermo Fisher’s TaqPath COVID-19 CE-IVD RT-PCR Kit, which received CE-IVD Mark in March 2020.
The high throughput diagnostic assay, compatible with the Amplitude platform, also received Interim Order Authorization from Health Canada on January 21. Thermo Fisher has secured a contract with a large provincial authority in Canada for Amplitude systems to help fight the pandemic.
Quest Gets CDC Contract for Mutation Identification
Quest Diagnostics has received a contract from the U.S. Centers for Disease Control and Prevention (CDC) to provide genomic sequencing for a project aimed at identifying new mutations and patterns of transmission of SARS-CoV-2.
The company did not disclose financial terms of the deal.
Ellume Nets $231 M Contract
Ellume became the first Food and Drug Administration–approved antigen test that can be used at home without a prescription. The test includes a sterile Nasal Swab, a Dropper, Processing Fluid, and a Bluetooth® connected Analyzer for use with an App on the user’s smartphone. Utilizing the dedicated App, the user follows step-by-step instructions to perform the test including a self-collected mid-turbinate swab. On Monday, HHS announced the US has awarded a $231 million contract Australia-based Ellume to ramp up production of its at-home coronavirus test — with 8.5 million tests. The sample is analyzed and results are automatically transmitted to the user’s smartphone via Bluetooth®. Results can be shared with healthcare professionals to enable optimal therapy. Through a secure cloud connection, the Ellume COVID-19 Home Test provides real time reporting of test results and critical data to health authorities, employers and educators, for efficient COVID-19 mapping.
Ellume’s test, which is expected to cost about $30, is similar to a home pregnancy test, if somewhat more high-tech: The user collects a sample with a nasal swab and then puts it into a digital analyzer linked to a smartphone app, through which results are delivered 15 minutes later.
COVID-19 One Year Later
It all started with ominous reports at the end of 2019 about a highly contagious virus that had emerged in Wuhan, China, seemingly a world away. But a few months later, many aspects of life across the globe would be in shambles, and lab medicine professionals would find themselves at the center of the worst public health crisis in 100 years.
FULL STORY on LabPulse.com -https://www.labpulse.com/index.aspx?sec=sup&sub=mic&pag=dis&ItemID=801941
The earliest stories in LabPulse.com about SARS-CoV-2 included a news item on January 17 about the publication of the full genome of the novel coronavirus and screening of air travelers coming in from Wuhan, per guidance from the U.S. Centers for Disease Prevention and Control (CDC).
One year later, LabPulse.com interviewed leaders in lab medicine for a look back at what went right — and what went very wrong — as the specialty dealt with the COVID-19 pandemic over the course of 2020.
No one was prepared
When did the magnitude of the COVID-19 pandemic become apparent for lab medicine professionals? For Dr. David Grenache, PhD, president of the American Association for Clinical Chemistry (AACC), it started to really sink in at the end of February, seeing how the outbreak was playing out in Italy and with cases already being reported in the U.S.
The scale of the crisis was becoming readily apparent from February to March, commented Dr. Patrick Godbey, president of the College of American Pathologists (CAP). But Godbey said it really hit home for him on March 10, with a report of the first case at a site affiliated with Southeastern Pathology Associates in Brunswick, GA, where he serves as president and CEO.
“A lot of things changed after that point,” Godbey said.
Meanwhile, diagnostics companies were hit in parallel and caught off guard. Manufacturers had been aware of the risk for emerging diseases, including flu pandemics, but more in the sense of being watchful as opposed to fully prepared, commented Bruce Carlson, publisher of market research firm Kalorama Information. Their thinking had been shaped by experience with prior outbreaks like bird flu, Zika, and Middle East respiratory syndrome (MERS), all of which were mostly manageable.
“Nobody was prepared at any level — not labs, not governments, not diagnostic companies — for a pandemic of this size,” Carlson said.
With the hard times came a better appreciation of how hard it is to turn out good, reliable lab results as quickly as possible in the most cost-effective manner possible, Godbey said. In the case of COVID-19, if a patient came in with a fever or cough, it was up to the lab to determine if that patient needed to be isolated.
“I am sorry that it took a pandemic to remind people of this, but the vast number of decisions are made on work that comes out of the laboratory,” Godbey said.
Labs needed to quickly learn how to communicate with a myriad of healthcare delivery providers, said Grenache, who is chief scientific officer at Tricore Reference Laboratories in Albuquerque, NM.
“Many healthcare systems realized that the laboratory was such a vital component to addressing their testing needs that they had to engage the laboratory at much higher levels of discussion,” Grenache said. “Working out the kinks in communication strategies between healthcare delivery systems and laboratories took some time and finesse.”
In addition to implementing testing for SARS-CoV-2, pathologists and other lab professionals shared information about tests early through preprint publications, helping move the community forward through the pandemic, said Dr. Gary Procop, chair of the American Society for Clinical Pathology’s (ASCP) commission on science, technology, and policy. They were also on the forefront of getting convalescent plasma from recovering patients, which was in short supply as a treatment for the virus, Godbey said.
Early in the pandemic, major IVD companies like Abbott and Roche ramped up production quickly, and Quest and LabCorp were able to roll out tests to detect infection with the SARS-CoV-2 virus, but it was not enough to match the huge demand, Carlson commented. In the past, outbreaks had been somewhat predictable based on demographics; but all of a sudden, a good portion of the population could potentially contract the virus and require testing, a big shift from more isolated outbreaks of the past.
This was difficult to prepare for, particularly as the testing effort for COVID-19 required molecular tests, which are very sophisticated and require trained personnel as well as products that involve intense biological production, Carlson said. Both labs and diagnostics companies faced overwhelming demand for molecular tests, and at the same time saw a huge decrease in volume and revenue for clinical chemistry tests, he added.
What went wrong
During the pandemic, the requirement for CLIA-certified labs to get emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) in order to make their own laboratory-developed tests (LDTs) for COVID-19 was a big barrier.
Initially, a test developed by the CDC was the only one with an EUA, and the agency initially shipped faulty test kits to public labs. During one session at the AACC 2020 annual meeting, held virtually in December, Morgan Pence, PhD, reflected on the difficulty community hospital labs had in getting an EUA, causing them to wait for a commercial assay instead.
Turnaround times for molecular tests were long and some began offering serology testing, recalled Pence, director of clinical and molecular microbiology at the Cook Children’s Medical Center in Fort Worth, TX, during his AACC presentation.
But in contrast to the restrictions on diagnostic tests, the FDA regulations on commercial antibody tests had been loose, and a flood of products entered the market, many with questionable accuracy. The FDA responded in May, announcing it was tightening regulations on commercial antibody tests.
The issues with antibody tests that the specialty was grappling with in the spring of 2020 have largely gone away since then, Grenache said.
“With time, people realized antibody tests by themselves were really not very useful — they weren’t clinically actionable,” he said.
As for LDTs, the U.S. Department of Health and Human Services released guidance on August 19 allowing labs to run their own tests without an EUA. But during professional association meetings at the end of the year, a common refrain from speakers was that this was too little too late.
The genome of the SARS-CoV-2 virus was available early on, and CLIA-certified laboratories are highly skilled at developing tests with this information, noted Procop, who is a pathologist at Cleveland Clinic. When the regulatory policy changed, labs had to rush to catch up.
“That clearly cost us a lot of time. That was a major misstep by our country and that should be addressed going forward,” Procop said. “We should not have some of the brightest minds in the world having to respond to a pandemic with one arm tied behind their back.”
Another much-cited failure during the COVID-19 pandemic was disruption of the supply chain, as reported in surveys by CAP and other lab medicine organizations, which resulted in a lack of swabs, transport media, and reagents. Admiral Dr. Brett Giroir, who led the testing efforts during the Trump administration, acknowledged persistent supply shortages during a special session at the AACC 2020 meeting.
The national supply chain should be able to provide all the materials for testing, without the need to resort to alternative strategies, such as pooling, Procop said.
“Necessity is the mother of invention,” but if there were appropriate supplies, labs wouldn’t have needed to go down those paths, Procop said.
Procop also sees the lack of a national testing strategy in the U.S. as a failure. COVID-19 response efforts, including testing and reopening, were largely left up to states. There were 50 very good governors doing their best for their states in 50 different ways, Procop noted. In contrast, the ASCP has been advocating for a strong national approach guided by the top experts in various fields of diagnostics.
As of January 31, over 26 million cases of COVID-19 had been reported in the U.S., with more than 440,000 deaths nationwide, according to the Johns Hopkins Coronavirus Resource Center. Variants discovered through surveillance efforts in South Africa and the U.K. and the pace of the vaccine rollout have been raising alarm.
President Joe Biden has pledged a federally directed effort against the pandemic that includes a call to “ensure all Americans have access to regular, reliable, and free testing.” His administration’s plan includes a doubling of the number of drive-through testing sites, investment in at-home tests, and the creation of a Pandemic Testing Board. CAP recently issued a statement on Biden’s plans, encouraging greater coordination and management of testing supplies.
Visby gets $12M to make flu/COVID-19 self-tests
Visby Medical has received $12.3 million in U.S. government funding to speed up the development of its rapid, single-use flu/COVID-19 polymerase chain reaction (PCR) test for at-home use.
The test detects the flu and/or COVID-19 using one handheld rapid PCR test for point-of-care use. Eventually, it will be available in consumers’ homes as an over-the-counter test.
The Biomedical Advanced Research and Development Authority (BARDA), an agency in the U.S. Department of Health and Human Services, awarded Visby the funds. The funding may be extended for a total of up to $48.7 million over a period of 38 months.
Protein biosensors show promise for SARS-CoV-2 testing
Scientists have developed biosensors to detect SARS-CoV-2 proteins and antibodies in simulated nasal fluids and human sera, according to a study published in Nature on January 27. The approach promises to be less costly and time-consuming than current COVID-19 testing methods.
Biosensors are devices used to detect the presence or concentration of specific biomolecules or biological structures. In this case, the researchers designed protein-based biosensors that recognize specific molecules on the surface of a particular virus and bind to them, then emit light through a biochemical reaction.
The scientists applied this approach to design biosensors of antibodies against SARS-CoV-2 protein epitopes and of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein.
The result was a biosensor that glows when mixed with COVID-19 antibodies.
The researchers were able to demonstrate that their SARS-CoV-2 biosensor does not react to other antibodies that might also be in the blood, including those that target other viruses, which is an important consideration for avoiding false-positive test results.
An illustration of a new biosensor binding to a targeted molecule and emitting light
An illustration of a new biosensor binding to a targeted molecule and emitting light. Image courtesy of Ian Haydon/Institute for Protein Design at the University of Washington.
The researchers hope that their approach will lead to faster testing in clinical settings. Currently, SARS-CoV-2 infections are routinely diagnosed using reverse transcription polymerase chain reaction (RT-PCR). However, RT-PCR is a slow process that relies on specialized skills and equipment in the laboratory. Furthermore, the COVID-19 pandemic has created shortages in lab supplies and other supply chain issues that slow down patients’ test results even further.
In contrast, luminescence-based protein biosensors offer an attractive approach to testing, particularly at the point of care, because they promise a nearly instantaneous readout. Furthermore, the quantification of luminescence can be carried out with inexpensive equipment such as a cell phone camera.
“We have shown in the lab that these new sensors can readily detect virus proteins or antibodies in simulated nasal fluid or donated serum,” said David Baker, PhD, director of the Institute for Protein Design at the University of Washington, in a statement. “Our next goal is to ensure they can be used reliably in a diagnostic setting. This work illustrates the power of de novo protein design to create molecular devices from scratch with new and useful functions.”
In addition to their biosensor model for detection of SARS-CoV-2, the scientists also demonstrated that similar models can be designed to detect proteins associated with cancer, namely human epidermal growth factor receptor 2 (HER2, breast cancer) and B-cell lymphoma 2 (BCL-2, lymphoma), and to detect hepatitis B antibodies.
COVID-19 testing boosts molecular point-of-care market
By Bruce Carlson, LabPulse.com contributing writer
January 27, 2021 — In 2021, Kalorama Information, sister publication to LabPulse.com, estimates the market for molecular point of care (mPOC) diagnostics will be worth $900 million. Not surprisingly, COVID-19 is the major factor in market growth and is the largest component of the market, with products such as POC immunoassays for COVID-19 expected to see technological advancements.
Molecular POC diagnostic solutions offer improvements in the sensitivity and specificity of existing near-patient and rapid tests while expanding the diagnostic capabilities at points of care such as hospital critical care units, physician offices, outpatient clinics, and community health posts in the developing world, and are used to assess conditions or admit patients. The concept of mPOC is to combine the accessibility of POC testing with the accuracy of molecular technology.
Kalorama defines mPOC as near-patient polymerase chain reaction (PCR), sequencing, or other nucleic acid testing (NAT) systems that offer small instrument size, near-patient placement, and fast turnaround of tests. The definition also covers tests that are CLIA-waived or tests that require a lower threshold of operational training so that they may earn CLIA waivers in the next five years.
A few examples of mPOC systems include Cepheid’s GeneXpert, Abbot’s IDNow, Roche’s Cobas Liat, and BioMerieux’s BioFire.
Before COVID-19, molecular systems needed to prove marginal worthiness as they are more expensive than other types of POC testing. The report indicates that at present COVID-19 has resulted in a huge acceleration in both system installations and spending on consumables per system. Cepheid’s installed base increased by around 30% in 2020 and sales of bioMerieux’s systems increased from around 600 per quarter. Spending per system was reported by many companies to have increased around 50%-60%.
Nonetheless, this surge is likely to be temporary. COVID-19 testing volumes should decrease regardless of whether the vaccines are fully effective. Volumes are expected to dip back within two years and taper to a level not very distant from previous forecasts. New systems will lead to increased usage since they provide motivation for additional testing.
Kalorama ‘s findings are in its report, “Market and Future Potential for Molecular Point of Care.”
Kalorama has covered the mPOC segment on a yearly or biyearly basis since 2013. Outside of COVID-19, the mPOC market is overwhelmingly in the respiratory category, with most of that dedicated to influenza testing. Other tests include hemagglutination inhibition (HAIs) tests and those for sexually transmitted infections (STIs), among other conditions.
Less than 10 years since the launch of these systems, Kalorama finds a marketplace with a real foundation in at least one testing segment, respiratory, but still with more potential than markets in other areas. The molecular POC diagnostics market detailed in the report includes sales of clinical IVD systems (tests, consumables, and instruments) used outside of central clinical laboratories such as hospital laboratories and reference or independent laboratories. Molecular diagnostics includes tests that detect or interrogate nucleic acid analyte sequences using processes such as nucleic acid amplification, hybridization with oligonucleotide probes, and nucleic acid sequencing.
The instrument placements that mPOC earned in 2020 should continue to pay dividends for companies in the future. Present in laboratories, mPOC systems can be put to work for influenza and antibiotic reduction even if the COVID-19 threat were to pass, which so far seems a long time away.
Bruce Carlson is the publisher of Kalorama Information, part of Science and Medicine Group. Kalorama’s market report on molecular point of care can be found on Kalorama’s website.
Thermo Combo COVID-19, Flu, RSV Test Earns CE Mark
Thermo Fisher Scientific announced it received CE-marking for its TaqPath COVID-19, Flu A/B, RSV Combo Kit for SARS-CoV-2, influenza A/B, and RSV. Thermo indicated the test for the diseases generates results in approximately three hours. Test results are analyzed using the Applied Biosystems Pathogens Interpretive Software, which automatically converts genetic analysis data into a report, which Thermo said reduces risk of interpretation errors.
Roche Antibody Test EUA
Roche today announced that its Elecsys® Anti-SARS-CoV-2 S antibody test has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). The semi-quantitative serology (blood) test can be used to measure the level of antibodies in people who have been exposed to the SARS-CoV-2 virus. The company says new test targets antibodies that are directed against the region of the novel coronavirus known as the spike protein, specifically the area that enables the virus cell to bind to the host cell receptor, which is required for the virus to enter the host cell.1,2 The test also provides a numerical result from 0.40-250 U/mL as well as a qualitative result.
The move is aimed at vaccine use: Many current candidate vaccines aim to induce an antibody response against the SARS-CoV-2 spike protein. Tests that quantify antibodies to the spike protein could be used to measure the level of that response and track that measurement over time.
Antigen Testing a Focus
In its COVID-19 Update report, Kalorama Information said that volume was up in labs and among IVD vendors, new technologies are available. Kalorama projects a 10.5 billion-dollar market for COVID-19. This is a 1 billion dollar increase from previous estimates.
For most aspects of the diagnostic testing process, there has still been a learning curve for all involved. Even in the fall of 2020, there are capacity limitations, questions about testing accuracy, and challenges with sample collection. But creative solutions have been emerging at labs to help ease the load during a difficult time. With over a million deaths worldwide, the COVID-19 crisis has continued to unfold with great challenges for the healthcare system and its suppliers.
Although a sensitivity of roughly 80% seems striking as a low number, in fact the negative predictive value can still be sufficient if the disease prevalence is appropriately matched. – Kalorama report
Rapid antigen tests are one of the factors driving growth; these tests can offer some major benefits in the effort to control the SARS-CoV-2 pandemic. The decision to apply antigen tests in certain situation as opposed to others is complicated and is still being completely sorted out. The decision to apply antigen testing depends on variables including:
- Sensitivity and specificity of the test
- Prevalence/ outbreak of COVID-19 in the given population
- Remote location, availability of laboratories/ hospitals
- Turnaround time of the test
- Cost of the test
- Ability to perform serial testing
The momentum of cases and tests, since our Kalorama’s COVID-19 Update in May has not slowed, sadly. There are over 45 million cases worldwide; 9 million of them in the United States. The trend is troubling as well, and there are fears of increases as the U.S. influenza season has arrived. (perhaps mitigated, perhaps not by reports of a milder flu season based on the experience in the southern hemisphere).
The scarcity of various diagnostic test related products during the COVID-19 pandemic has further driven home the reality that different testing methods are best allocated for different situations. While antigen tests have been criticized for the lower performance characteristics compared to antibody and molecular tests, these metrics are not always the most significant. Antigen tests often can have sensitivity lower than 85% while the specificity needs to be fairly high, in the range of 98% or higher. Although a sensitivity of roughly 80% seems striking as a low number, in fact the negative predictive value can still be sufficient if the disease prevalence is appropriately matched.
Marketed tests include:
- Abbott Laboratories -BinaxNow COVID-19 Ag Card & Navica app
- Access Bio -CareStart COVID-19 Antigen
- BD-BD Veritor System for Rapid Detection of SARS-CoV-2
- BIOHIT -HealthCare SARS-CoV-2 Antigen Rapid Test Kit
- Confirm BioSciences -Verasure COVID-19 Antigen Rapid Swab Test
- Dynamiker Biotechnology – Dynamiker SARS-CoV-2 Ag Rapid Test
- Edinburgh Genetics – ActivXpress+ COVID-19 Antigen Complete Testing Kit
- FenHe Technology -reOpenTest COVID-19 Rapid Antigen Test
- JOYSBIO Biotechnology – COVID-19 Antigen Rapid Test Kit (Colloidal Gold)
- LumiraDx – SARS-CoV-2 Ag Test
- Menarini Diagnostica/ Boditech Med – iChroma COVID-19
- OraSure Technologies – at-home test
- Roche – SARS-CoV-2 Rapid Antigen Test
- Sensitest – Corona Antigen Rapid Test
- Sona Nanotech – Sona COVID-19 Rapid Antigen Test
- Tigsun Diagnostics – COVID-19 Antigen Saliva Rapid Test
Unique and Proprietary Technologies
In addition to the standard formats such as lateral flow and ELISA, there are also a number of unique technologies being applied for SARS-CoV-2 antigen testing. These include the following examples of companies and their products/ technologies that are either available or in development:
- AmonMed Biotechnology – Rare Earth Nano Fluorescence Immunochromatography Avacta/ Adeptrix with Cytiva (Danaher) – working on rapid
- POC saliva test for self-testing and large scale population screening
- Celltrion – Magnetic Force-assisted Electrochemical Sandwich Immunoassay (MESIA) technology – CLIA high and medium complexity
- E25Bio – paper based nasal swab test
- Ellume – working with Qiagen on test cartridges for home use, POC, and high throughput system
- Genspeed Biotech – micro-ELISA
- Luminostics – antigen immunoassay that uses glow-in-the-dark nanomaterials
- New Gene (Hangzhou) Bioengineering – novel ligand-receptor chromatography test kit
In October, the FDA provided a template to help test developers applying for EUA for SARS-CoV-2 antigen tests. The template provides a range of recommendations as well, for example in order to show the test suppliers how to handle their validation data. Many of these are suggested but not required. The template recommends that antigen tests should have a sensitivity of at least 80%, but noted that serial testing could allow for results of lower-performing tests (e.g. 70% sensitivity) to be calculated cumulatively.
Qiagen releases portable SARS-CoV-2 antigen test
Qiagen has launched a portable, digital SARS-CoV-2 antigen test that can analyze more than 30 swab samples per hour. The company developed the QIAreach SARS-CoV-2 antigen test in collaboration with the Australian firm Ellume. The test processes samples in two to 15 minutes. Qiagen is marketing and distributing it in the U.S. and has applied to the U.S. Food and Drug Administration for emergency use authorization. It has also applied for the CE-IVD Mark for the European Union.
Hologic Q4 sales boom on diagnostics revenues
Booming revenues in its Molecular Diagnostics segment due to the COVID-19 pandemic helped Hologic post a 55.6% increase in sales for its fourth quarter. The company also swung into the black compared with a net loss in the same period the year before. For the fourth quarter (end-September 26), Hologic recorded revenues of $1.3 billion compared with $865.8 million in the same quarter last year. The increase was bolstered by the company’s Worldwide Molecular Diagnostics revenue, which increased by 375.8% to $818.9 million, due to demand for its SARS-CoV-2 assays.
Net income for the quarter was $493.6 million, compared with a net loss in 2019 of $123.5 million. For the year, Hologic posted revenue of $3.776 billion, up 12% compared with $3.367 billion in 2019. The company’s net income for the year was $1.1 billion, compared with a $203.6 million net loss last year.
BD posts healthy global, U.S. Q4 revenues
Becton Dickinson (BD) has reported worldwide fourth quarter revenues of $4.8 billion (end-September 30), up 4.4% compared to the same period in 2019. U.S. revenues increased 7.4%, to $2.7 billion. The company’s COVID-19 testing sales totaled more than $440 million for the quarter, it said. Its Life Sciences segment posted revenues of $1.5 billion, up 31.2% compared to the same period last year. However, the company’s Medical segment posted worldwide revenues of $2.3 billion, down 4.9% from 2019, and its Interventional segment revenues decreased 3.4% compared to 2019, at $978 million, which BD attributed in part to the impact of COVID-19.
CMS to cut COVID-19 payments to slower labs
October 16, 2020 — In a bid to speed up COVID-19 testing, the U.S. Centers for Medicare and Medicaid Services (CMS) has announced a new policy to pay for expedited COVID-19 test results. Starting January 1, Medicare will pay $100 only to labs that complete high-throughput COVID-19 diagnostic tests within two calendar days of specimens being collected.
Under the new policy, labs that take longer than two days to complete COVID-19 tests will be paid $75 — a 25% pay cut.
Back in April, CMS increased payment from $51 to $100 for COVID-19 tests. The amended ruling lowers the base payment for COVID-19 diagnostic tests run on high-throughput technology to $75, but CMS will add on $25 for labs on two conditions:
The lab completes the test in two calendar days or less
The lab completes the majority of its COVID-19 diagnostic tests that use high-throughput technology in two calendar days or less for all its patients (not just Medicare ones) in the previous month.
CMS established these requirements to spur faster high-throughput COVID-19 diagnostic testing not only for Medicare patients, but for all patients, the agency said.
The new proposal is already drawing fire from lab medicine groups, however. The College of American Pathologists (CAP) characterized the new policy as a pay cut and said that the policy would penalize labs for delays that in many cases are outside their control.
“The CAP urges the CMS to cease implementation of this misguided fee structure and answer our repeated calls to take steps to support pathologists and laboratories by increasing Medicare rates for COVID-19 tests,” said CAP President Dr. Patrick Godbey, in a press statement.
New AMP Survey Released: Staffing, Supply Chain are Issues For Labs
The Association for Molecular Pathology (AMP) has released the preliminary results of its August 2020 SARS-CoV-2 testing survey for clinical laboratories showing labs continue to experience supply chain interruptions and are now also facing significant staffing shortages. However, the demand for molecular diagnostic testing has increased.
More than half (54%) of the respondents said testing demand was currently higher than their capacity, and they anticipate demand will continue to rise, especially with the fall and winter influenza season.
While demand keeps rising, staffing has not — 85% of respondents have shortages and 66% do not have enough qualified clinical laboratory technologists/scientists. In addition, more than half (53%) do not have enough clinical laboratory technicians.
Based on the most recent survey results, as well as an earlier April survey, the AMP has two new recommendations:
- Ensure that regulatory requirements are not duplicative or burdensome. Keep the U.S. Centers for Medicare and Medicaid Services (CMS) as the regulatory agency responsible for lab oversight, as specified by the CLIA program.
- Support laboratory workforces through better collaboration and communication between public health, clinical laboratories, and relevant government agencies.
AMP’s previous five recommendations still stand, which are the following:
- Reassessing the type and location of SARS-CoV-2 testing services needed
- Reprioritizing supply allocations based on clinical testing needs
- Increasing transparency, communication, and real-time transmission of information between laboratories and suppliers
- Ensuring real-time coordination among laboratories to offset excess capacity
- Standardizing agency reporting format and processes
AMP will continue to review the pandemic’s impacts on clinical practice, regulatory policy, and reimbursement.
“These survey results will be fundamental to informing potential legislation and other initiatives that could significantly improve response to the current and future pandemics,” said Dr. Karen Weck, AMP president and director of the molecular genetics lab at the University of North Carolina Chapel Hill.
Paragon debuts more COVID-19 NGS tests
Precision medicine firm Paragon Genomics has debuted two additional CleanPlex next-generation sequencing (NGS) tests to detect the novel coronavirus and estimate disease severity. The tests include the CleanPlex angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) panel, a multiplex polymerase chain reaction (PCR)-based targeted sequencing assay that analyzes genetic factors impacting COVID-19 infection susceptibility and disease severity. In addition, the CleanPlex SARS-CoV-2 Flex research panel detects mutations and additional genome coverage of the novel coronavirus.
The panels add to Paragon’s existing ClearPlex SARS-CoV-2 Research and Surveillance Panel, which allows SARS-CoV-2 genome sequencing for accurate nucleic acid-level data. The ClearPlex RNA workflow converts viral RNA into libraries ready for sequencing in hours, according to Paragon.
The company also announced plans to introduce new CleanPlex PCR primers in order to expand the capability of its NGS panels for the novel coronavirus. The primers will allow researchers to run up to 3072 CleanPlex sequencing samples simultaneously on Illumina NovaSeq instruments, the company noted.
In addition, Paragon said it will release an early-access edition of its CleanPlex Respiratory Research Panel next week. The panel combines diagnostics for the novel coronavirus, both flu strains, and H1N1, H1N2, and H3N2.
Beckman Coulter Nabs EUA
October 9, 2020 — The U.S. Food and Drug Administration (FDA) has granted emergency use authorization (EUA) to Beckman Coulter’s Access SARS-CoV-2 immunoglobulin M (IgM) assay, which detects antibodies that recognize the receptor-binding domain (RBD) of the spike protein on the virus.
The firm is also developing a SARS CoV-2 antigen assay as well as a quantitative IgG assay that it anticipates will be launched later this year.
FDA authorizes Abbott’s COVID-19 real-time antigen test
August 27, 2020 — The U.S. Food and Drug Administration (FDA) has issued an emergency use authorization for a COVID-19 antigen test developed by Abbott Diagnostics Scarborough from which results can be read directly from the testing card.
A nasal sample from the patient is placed on Abbott’s BinaxNow COVID-19 Ag Card and a reagent is added; after 15 minutes, the results appear, with one line indicating a negative result and two lines a positive. The test has shown a sensitivity of 97.1% and specificity of 98.5%, according to the FDA.
Abbott’s BinaxNow COVID-19 Ag Card can be used in doctor’s offices, emergency rooms, or perhaps even schools, according to the FDA. The company plans to make a free phone app available for the test which will allow patients to display their test results when asked by organizations like workplaces and schools. It also plans to make up to 50 million of the tests available in the U.S. each month by October.
“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,” Shuren said.
Abbott said it planned to sell the BinaxNow test for $5. The test uses the company’s lateral flow technology, which makes it reliable and a familiar format for frequent mass testing, according to Abbott. Because it does not require equipment, the BinaxNow test will help healthcare providers quickly identify those who are infected with SARS-CoV-2 so they don’t spread the disease to others, the company noted. It can also be used in the point-of-care setting.
COVID-19 Diagnostic Testing Friend and Foe to IVD Company Revenues
Any assumption that COVID-19 testing would boost company revenues universally has been put to rest as revenues came out. The reduction in activities that drive testing has lead to drops in traditional in vitro diagnostics formats. Thus there are mixed results in the first quarter of this year that reported on three full months of the diseases presence in the United States. Reviewing recent Q2’s from in vitro diagnostic companies, generalist companies have suffered while specialists in molecular and antibody and respiratory specialists have performed well.
Abbott Diagnostics’ worldwide sales took a hit despite bringing in about $615 million in revenues from COVID-19 diagnostic testing during the second quarter of 2020 (end-June 30, 2020). The company reported sales dropped 8.2% to $7.3 billion in the second quarter of 2020, compared to $7.97 billion during the same period in 2019. Furthermore, net earnings dropped dramatically. Income fell about 46.6% to $537 million in the second quarter of 2020. That compares to net earnings of $1.006 billion in the second quarter of 2019.
Quidel announced that revenue in its second quarter (end-June 30) has skyrocketed due to sales of COVID-19 tests. Q2 revenue increased 86% from $108.3 million in 2019 to $201.8 million with sales of its COVID-19 tests accounting for $109 million of the growth. Specifically, rapid immunoassay product revenue increased 270% in the company’s second quarter to $80.6 million, primarily due to $56.3 million in revenue for Quidel’s Sofia severe acute respiratory syndrome (SARS) Antigen test. Similarly, revenue from molecular diagnostic solutions increased $51.0 million to $55.2 million due to the Lyra SARS-CoV-2 assay, which brought in $52.7 million in sales. However, revenue from cardiometabolic immunoassay products dropped 20% to $54.2 million due to reduced hospital visits by chest pain patients stemming from the COVID-19 pandemic. Also, specialized diagnostic solutions revenue decreased 18% to $11.8 million.
Quidel’s net income for the second quarter of 2020 reached $67.7 million, compared with a net income of $1.3 million for the second quarter of 2019. The firm showed a similar pattern of an increase in sales as well as income for the six months ended June 30. Total revenue reached $376.4 million versus $256.2 million for the same period in 2019, again driven by COVID-19 products. Net income for the six-month period shot to $107.9 million as compared with net income of $26.1 million for the same period in 2019.
Bio-Rad Negative Second Quarter Results
Bio-Rad Laboratories reported that the COVID-19 pandemic negatively impacted its revenue for the second quarter (end-June 30) as well as for the first half of the year. Sales dropped 6.2% to $536.9 million compared with $572.6 million for the second quarter of 2019. In particular, revenues in the company’s clinical diagnostics segment decreased by 20.7%. However, net income for Q2 was $966.4 million versus $598.8 million in the second quarter of 2019 primarily due to the recognition of changes in the fair market value of equity securities related to the holdings of Bio-Rad Laboratories’ investment in Sartorius.
Year-to-date net income reached $1.65 billion compared with $1.46 billion for the same period last year. Given the situation with the pandemic, the firm thinks its third quarter 2020 year-over-year currency-neutral sales may be flat to up 5%.
FDA grants Vela EUA for SARS-CoV-2 test
The U.S. Food and Drug Administration (FDA) has granted emergency use authorization (EUA) to Vela Diagnostics for the manual version of its coronavirus polymerase chain reaction test. The ViroKey probe-based reverse transcription PCR (RT-PCR) test detects SARS-CoV-2 by targeting conserved regions of the viral genome. The test detects SARS-CoV-2 in nasopharyngeal and oropharyngeal swabs, and the manual version allows for flexible sample processing and quick adoption of the test by laboratories with existing Applied Biosystems 7500 Fast Dx instruments, Vela Diagnostics said. Vela also developed an automated version of the assay for use with the Sentosa SX101 instrument in combination with the 7500 Fast Dx PCR instrument or the Sentosa SA201 instrument.
On top of the EUA from the FDA, the ViroKey SARS-CoV-2 RT-PCR test has also received the CE-IVD Mark and provisional approval from the Singapore Health Sciences Authority, the firm said.
Biomarkers to determine COVID-19 odds: GW researchers
George Washington (GW) University researchers have found five biomarkers associated with higher odds of clinical deterioration and death in COVID-19 patients.
A research team led by Dr. Shant Ayanian, an assistant professor of medicine at the GW School of Medicine & Health Sciences, evaluated 299 patients diagnosed with COVID-19 and admitted to GW Hospital between March 12 and May 9 (Future Medicine, July 17, 2020). More than two-thirds (200) of the patients had all five biomarkers evaluated: interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin. Elevated levels of the biomarkers were associated with inflammation and bleeding disorder, showing an independent increased risk for intensive care unit admission, invasive ventilatory support, and death.
However, two biomarkers demonstrated the highest odds of death: when LDH was more than 1,200 units/L and D-dimer levels were greater than 3 µg/mL. Instead of determining COVID-19 deterioration and death risk solely by age and other factors, a blood test can support clinical decision-making, the group concluded.
New Players in COVID-19 Testing
Eli Lilly, Promega, Others Enter the Fray
Eli Lilly and Company (NYSE:LLY) will offer drive-through testing for SARS-CoV-2, the virus that causes COVID-19, to Indianapolis area health care workers beginning Monday, March 23, as a service to the community and in an effort to protect health care providers working on the front lines during this epidemic.
Lilly announced last week that the company is working with the Indiana State Department of Health to offer testing of COVID-19 samples acquired at local hospitals, using a specialized facility at Lilly Research Laboratories. Now Lilly is expanding the service to the community by offering drive through-testing at Lilly’s Indianapolis headquarters. At this time, only active health care workers are eligible, and they must have a physician’s order requesting testing for COVID-19. There will be no charge for this service.
Promega applied to the U.S. Food and Drug Administration for an emergency use authorization (EUA) for its new serological antibody test for COVID-19, Lumit Dx. The SARS-CoV-2 immunoassay is an IVD test that detects the presence of antibodies against SARS-CoV-2. Among patients whose COVID-19 was confirmed by polymerase chain reaction (PCR) 20-plus days after symptom onset, Lumit Dx has a sensitivity of 93.5% when used in patients with varying disease levels. It has a 100% sensitivity when used in hospitalized patients. It has a specificity of 99.4% in samples presumed negative for SARS-CoV-2 and 97.7% in samples exhibiting other illnesses, according to Promega. Lumit Dx requires no wash steps, offers reliable results in less than an hour, and is easily adaptable to most liquid handlers, according to the firm.
Austin-based Everlywell’s COVID-19 Test Home Collection Kit is now authorized to be used by individuals at home who have been screened using an online questionnaire that is then reviewed by a health care provider. The FDA also approved two diagnostic tests, performed at specific labs, for use with the samples collected by the kit.
Federal Mandates for Nursing Home COVD-19 Testing
President Trump announced several new Centers for Medicare and Medicaid Services (CMS) initiatives designed to protect nursing home residents from COVID-19, including new testing requirements.
Funding for the deployments is coming from the U.S. Department of Health and Human Services (HHS), which will devote $5 billion of the Provider Relief Fund authorized by the Coronavirus Aid, Relief, and Economic Security Act to Medicare-certified long-term care facilities and state veterans’ homes. The funds are in addition to the $4.9 billion previously announced to offset revenue losses and assist nursing homes with additional costs related to responding to the COVID-19 public health emergency and the shipments of personal protective equipment.
CRP Recommended for Steroid Use Assessment
The level of C-reactive protein (CRP) in the blood of coronavirus patients could help safely guide treatment with steroids, which have the potential to save many thousands of lives, researchers reported July 22 online in the Journal of Hospital Medicine.
Out of 1,806 patients who were hospitalized with COVID-19, 140 were treated early with steroid therapy — mostly prednisone, but also including some on dexamethasone and methylprednisolone — and did not suffer worse mortality or need mechanical ventilation.
But drilling down on the results, those whose CRP was high — defined as greater than or equal to 20 mg/dL — had significantly reduced risk of mortality or ventilation, and conversely, those with low or normal CRP — less than or equal to 10 mg/dL — had a higher risk for needing ventilation or dying. The CRP results were evident in analyses whether the data were adjusted or not adjusted for clinical characteristics of the patients.
“The public health implications of these findings are hard to overestimate,” Dr. Marla Keller, professor of medicine (infectious diseases) at Albert Einstein, and colleagues reported. “Given the global growth of the pandemic and that glucocorticoids are widely available and inexpensive, glucocorticoid therapy may save many thousands of lives.”
Furthermore, lives could be saved by knowing who shouldn’t get steroid therapy, they suggested.
Strength in subgroup analyses
The study was conducted to evaluate experience with systematic steroid treatment for the novel coronavirus in New York City, a hotspot during the pandemic, with 17,000 confirmed deaths as of early June, most commonly attributed to acute respiratory distress syndrome (ARDS). Mechanical ventilation has been associated with mortality and the role of steroid treatment has been unclear. There is some evidence supporting the use of dexamethasone for COVID-19 during the pandemic, but this class had not been thought to be beneficial for ARDS before the public health emergency. Among other things, researchers wanted to evaluate whether early steroid treatment could keep people alive and off ventilators.
The study presents outcomes for all patients hospitalized between March 11 and April 13 at four hospitals run by the Montefiore Medical Center in the Bronx.
“Because the outcomes of in-hospital mortality and in-hospital [mechanical ventilation] cannot be assessed in patients still hospitalized, we included only patients who either died or had been discharged from the hospital,” the authors explained.
The study also focused its inclusion criteria on those given glucocorticoids within 48 hours of admission versus those who were never treated with them. Subgroup analyses assessed certain biomarkers, such as CRP and D-dimer levels, the latter of which have also been associated with inflammation and severity of COVID-19.
“Our findings suggest a role for CRP to identify patients who may benefit from glucocorticoid therapy, as well as those in whom it may be harmful,” the authors wrote. “Additional studies to further elucidate the role of CRP in guiding glucocorticoid therapy and to predict clinical response are needed.”
The authors also noted that the results are in line with findings of the U.K. Randomised Evaluation of COVID-19 therapy (RECOVERY) study, which found a mortality benefit for hospitalized COVID-19 patients treated with the steroid dexamethasone.
FDA Instructs Labs to Remove Faulty Tests from Stock
The U.S. Food and Drug Administration (FDA) has advised labs not to use antibody tests for the novel coronavirus that have been found to have low performance and to remove them from stock. The agency has published a list of products that have been removed from the market, either voluntarily by manufacturers or by FDA requirement, and will be continually updating it on its list of frequently asked questions web page. In a letter to lab professionals and health providers on June 19, the agency said that tests on the “removed list” should be taken out of stock and that patients tested with them previously may need to be retested as the results may have been incorrect.
Whereas at the beginning of the COVID-19 pandemic, the FDA had lax rules on market entry for tests, allowing products to be sold without review by the agency, it introduced stricter requirements for performance criteria and timing on applying for emergency use authorizations in May. The FDA also recently revoked emergency use authorization for Chembio’s serology test.
Hundreds of Tests on The Market, U.S. Labs Mostly Use Ten
As the COVID-19 crisis surfaced in the United States, molecular diagnostic manufacturers went to work with new RT-PCR testing kits. There have been hundreds of tests on the market receiving EUAs from the Food and Drug Administration, but a survey from the Association of Molecular Pathology demonstrated that only a few are used by laboratories. As part of its survey: https://www.amp.org/advocacy/sars-cov-2-survey/ labs were asked their top ten testing methods. Among them: Abbott m2000, Roche cobas were the top two vendors in most labs’ top tens.
This makes sense, these systems are the ones in most laboratories and the ones that are set up for other RT-PCR uses such as testing for HIV. Other tests in labs’ Top Tens included: Cepheid Gene Xpert Roche cobas, Hologic Panther, DiaSorin Simplexa, Quidel Lyra, Thermo Fisher Taq Path, Abbott IDNOW, CDC Test. There’s still a market for innovators. Unique near-patient tests, sample collection methods such as saliva or self-test, NGS and mass spectrometry testing, multiple PCR test targets, improved antibody tests, high throughputs, extraction kit workarounds – these are all examples of areas that innovators can improve.
The survey also said that labs have had supply issues throughout the crisis, which they’ve mitigated by using other vendors.
AACC Weighs in on Self-Collection, Antibodies and Other COVID-19 Testing Issues
The American Association for Clinical Chemistry (AACC) has recently taken a position on a number of controversies that have come up as the nation ramps up testing. Most notably, it spoke in opposition to FDA’s at-home virus kit clearance, following the go-ahead for Everlywell’s kit. The American Association for Clinical Chemistry (AACC) has notified the U.S. Food and Drug Administration (FDA) that it objected to the agency’s recent emergency use authorization (EUA) of an “unproven” at-home coronavirus collection kit.
The FDA has been approving products related to SARS-CoV-2 rapidly through the EUA pathway. In a letter to FDA Commissioner Stephen Hahn, the AACC said that this haste has resulted in the “introduction of an unproven product into the market.” The letter referenced a product that received clearance on May 16, without noting a product or company name.
The FDA granted emergency authorization to Everlywell’s at-home nasal sample collection kit for COVID-19 testing on May 15, noting at the time that this is the only product of its kind authorized for use with multiple COVID-19 diagnostic tests.
In the letter to the FDA, President Carmen Wiley, PhD, said there is insufficient information about the quality of the product in the EUA.
“A review of the FDA’s EUA to this company does not indicate that adequate clinical studies were performed to validate the kit or that good manufacturing practices were followed to develop it,” she wrote. “Further, the company selling the kit is not a laboratory.”
Increasing access to home-use collection kits can expand testing capacity and meet the need for fast diagnoses, but inaccurate results can do more harm than good, she wrote, urging the FDA to improve transparency in its regulatory decisions.
“We urge the FDA to withdraw its approval of this EUA or release the underlying clinical information that served as the basis for its expedited review,” Wiley wrote. “Authorization for this test kit should not be granted until the FDA has received and assessed the missing information and has released these data to the public.”
AACC guidance also urged caution on rapid POC coronavirus tests. When using rapid point-of-care (POC) tests for the novel coronavirus, healthcare institutions need to monitor the proficiency of operators and make sure the quality of test results isn’t being sacrificed for speed, according to new guidance from the American Association for Clinical Chemistry (AACC) released June 4. The guidance document on the management of POC testing (POCT) is an update to the AACC’s laboratory medicine practice guidelines/evidence-based practice for POCT, which were published in 2006.
The revised document tackles the following questions:
- What is the value of an interdisciplinary committee to oversee POCT?
- Does education improve POCT performance?
- What is the optimal staffing model for POCT?
- Do proficiency testing/external quality assessment programs improve POCT performance and patient outcomes?
- Does data management improve POCT outcomes?
- How should staff select POCT devices?
- How does POCT improve process?
In a statement about the release, the AACC highlighted its views on POCT for COVID-19. Institutions should maintain ongoing training for POC operators, track areas that need improvement, and participate in proficiency testing and quality assessment, the AACC advised.
The organization noted problems with rapid tests during the pandemic. In mid-May, the agency alerted the public to problems with Abbott Diagnostics’s ultrarapid ID Now test for COVID-19, which delivers results in 15 minutes. The product will stay on the market, but negative results need to be followed up with a second test and the company needs to conduct postmarket studies to support performance.
“As transformative as these tests are … healthcare institutions need to exercise care in all aspects of their point-of-care testing programs to make sure they aren’t trading [high-quality] test results for speed,” the AACC said in a statement.
The American Association for Clinical Chemistry (AACC) is advising that antibody testing for the novel coronavirus should be limited to diagnostics that have emergency use authorization (EUA) from the US. Food and Drug Administration (FDA) or developed by a CLIA-certified lab.
The AACC also published its recommendations for antibody tests in a new document on May 18. The agency recently revised its policies on antibody testing to require products to get an EUA within 10 days, but there are still issues with test quality, the AACC advised.
“Before implementation of any antibody test, laboratory medicine professionals must also evaluate the test’s accuracy and reliability even if it already underwent FDA review,” the AACC said in a statement about its new recommendations.
The recommendations document includes metrics that may be used for evaluating antibody tests for the novel coronavirus. Antibody tests should not be used as the primary method for diagnosing acute infection or excluding infection in asymptomatic patients. The AACC has also addressed quality of antibody testing in educational videos.
The College of American Pathologists (CAP) also weighed in. CAP elucidated its position on serology testing in a statement from President Dr. Patrick Godbey. Antibody tests have been drawing scrutiny with the entry of a large number of tests that had not been reviewed by the U.S. Food and Drug Administration (FDA). Questions have arisen about quality and validation. The agency recently revised its policies to provide more oversight over antibody tests. CAP’s statement noted that the accuracy of available antibody assays and the clinical significance of positive results are unclear.
FDA Withdraws Chembio COVID-19 Authorization on False Negative Data
FDA has withdrawn Chembio’s EUA for its rapid antibody tests. Too many false negatives was the culprit, according to the agency. This was based on data submitted by the company and an independent evaluation by the National Cancer Institute showed the test generated a higher-than-expected rate of false results. The risk to public health from incorrect test results makes EUA revocation appropriate. The product may not be distributed.
This development highlights the temporary nature of an emergency authorization issued in a crisis, and It does highlight the need for manufacturers to engage in stress testing antibody tests with large numbers of samples prior to manufacture. A test with a high amount of false negatives could obviously be dangerous, and the FDA is showing they are serious about antibody testing and ensuring that only high-performance tests get to keep the EUA.
Chembio has been around a long time and they are POC emerging infectious disease experts with industry standard tests for Zika and Chagas. The company will likely be able to develop a test on a different platform.
The U.S. Food and Drug Administration (FDA) has published guidance for diagnostics developers that it said will enable broad diagnostic testing of asymptomatic people and sample pooling during the COVID-19 pandemic.
FDA paves way for mass coronavirus screening of asymptomatic people
The template updates provide guidance on validating molecular diagnostics for these purposes and getting them cleared through the agency’s emergency use authorization (EUA) pathway.
“The FDA recognizes that organizations may want to conduct screening of asymptomatic individuals as part of a broader strategy to help ensure the safety of their employees, patients, students and others,” the FDA explained in a June 16 statement.
Guidance on pooling samples during testing is intended as an aid during the pandemic, as it minimizes use of supplies, which have not been adequate. While mixing samples in a batch reduces the number of tests needed and saves on supplies, there is a greater risk for false-negative results. The technique works best when low prevalence of the coronavirus is expected.
“Given that testing asymptomatic individuals means testing a greater volume of patients, and a low prevalence may be more likely in an asymptomatic population, particularly if the population is at low risk for contracting COVID-19, developers may be interested in using pooling techniques in tests used for asymptomatic screening,” the agency said.
Information in the clinical laboratory test section of frequently asked questions has been updated to clarify the FDA’s thinking on testing of asymptomatic people. Most COVID-19 diagnostics that have EUAs from the agency were cleared for individuals with suspected infection. This covers people who are asymptomatic, presymptomatic, and symptomatic, with use guided by a healthcare provider.
Tests need to be specifically authorized by the FDA for broad screening of asymptomatic populations. For this purpose, a highly sensitive test is needed for the most accurate results, and point-of-care tests tend to be less sensitive than laboratory-based tests, according to the agency.
“Although current data suggests that asymptomatic and symptomatic individuals with COVID-19 may have similar levels of viral genetic material in their anterior nares and other upper respiratory sites, there is limited data on the viral loads at different timepoints, in asymptomatic and pre-symptomatic individuals,” the FDA advised.
Guidelines on diagnostic testing from the U.S. Centers for Disease Control and Prevention (CDC), which were last updated on June 13, mainly focus on people who are symptomatic or who have had a known exposure to the coronavirus. However, the CDC also has provided guidance on testing asymptomatic people without known exposure in certain settings where the coronavirus is a particular risk and where regular and broad testing of all may be a good idea, including long-term care facilities, and high-density critical infrastructure workplaces where continuity of operations is a high priority.
Ortho Clinical Diagnostics Nets $678,000 BARDA Grant for VITROS COVID-19 Total Antibody Tests
The Biomedical Advanced Research and Development Authority (BARDA) has awarded Ortho Clinical Diagnostics $678,000 in support of the company’s COVID-19 antibody testing program. Ortho’s total antibody test detects all COVID-19 related antibodies (IgA, IgM and IgG) and Ortho’s COVID-19 IgG antibody test detects the IgG antibody, which appears in a patient’s blood in the later phase of the infection and remains elevated even after recovery. The tests offer greater choice in tracking, surveillance and patient management. As noted on the U.S. Food and Drug Administration’s website, test results also can help aid in determining who may be eligible to donate a part of their blood called convalescent plasma, which may serve as a possible treatment for those who are seriously ill from COVID-19. The tests run on Ortho’s high-throughput, fully automated analyzers including its flagship VITROS® XT 7600 Integrated System, the VITROS® 3600 Immunodiagnostic System, the VITROS® 5600 Integrated System and VITROS® ECi/ECiQ Immunodiagnostic Systems.
Roche IL-6 Test Receives EUA
Roche announced it received EUA from the FDA for its Elecsys IL-6 test
which measures levels of IL-6 (interleukin-6), a protein that triggers the body’s immune and inflammatory response to fight infections. Because IL-6 is released so early during a severe infection, it helps physicians to identify severely ill COVID-19 patients as early as possible. High levels of IL-6 can cause the immune system to begin attacking itself, unleashing a cytokine storm, which has been linked to the deaths of a number of COVID-19 patients.
Roche’s Elecsys interleukin-6 (IL-6) test has received authorization for emergency use from the U.S. Food and Drug Administration (FDA) as a method for identifying COVID-19 patients who are having a severe inflammatory response. The emergency use authorization was granted on June 2 and Roche said that it is available for use on its cobas e analyzers, which are widely available globally. The test is available in countries that accept the CE Mark in addition to the U.S. The cobas analyzers offer throughput of 300 tests per hour and deliver results in approximately 18 minutes, according to the company. Elevated IL-6 levels can help alert health providers to patients who are critically ill and at high risk of developing respiratory failure and needing a ventilator, the company noted in a statement. T-cell exhaustion and cytokine storm have been documented in COVID-19 patients, spurring research into Roche’s IL-6 inhibiting antibody tocilizumab (Actemra) as a treatment.
Self Collection OK For Samples: Study
Specimens that were self-collected by COVID-19 outpatients produced diagnostic outcomes that were nearly identical to those from physician-collected samples in a Stanford University study published June 12 in JAMA Network Open. The results suggest that at-home self-collection is suitable for SARS-CoV-2 testing. For the study, researchers compared patient-collected lower nasal swabs with physician-collected nasal and oropharyngeal swabs to see if the collection methods would yield equivalent diagnostic outcomes. They enrolled 30 outpatients who had previously tested positive for SARS-CoV-2 on a reverse transcription polymerase chain reaction (RT-PCR) test. Three specimens (one patient-collected and two physician-collected) were taken in a drive-through testing setting at Stanford Health Care.
The authors noted that if self-collected and physician-collected swabs turn out to be diagnostically equivalent, patients would be able to collect specimens themselves, which could not only increase access to testing but also help reduce healthcare workers’ exposure risk and use of personal protective equipment. However, they cautioned that the results are limited by a small sample size and need to be validated in diverse clinical settings.
For 29 of the 30 patients, the self-collected samples yielded identical results (11 positive, 18 negative) as the physician-collected swabs. In the one mismatched result, the self-collected nasal specimen tested positive, whereas the physician-collected nasal and oropharyngeal swabs both tested negative. This suggests sensitivity of 100% and a specificity of 95% for the self-collected swabs, according to Dr. Yvonne Maldonado and colleagues, who reported their findings in a research letter. The physician-collected nasal and oropharyngeal swabs yielded the same results for all 30 patients.
The authors noted that if self-collected and physician-collected swabs turn out to be diagnostically equivalent, patients would be able to collect specimens themselves, which could not only increase access to testing but also help reduce healthcare workers’ exposure risk and use of personal protective equipment. However, they cautioned that the results are limited by a small sample size and need to be validated in diverse clinical settings.
Commercialization of at-home coronavirus specimen collection has had a bumpy ride. The U.S. Food and Drug Administration (FDA) has granted emergency use authorization for a handful of at-home nasal sample collection kits for COVID-19 testing, including offerings by LabCorp, Quest, and PrivaPath Diagnostics.
However, some tests were marketed to consumers prior to gaining FDA authorization, drawing scrutiny about product quality. In May, the American Association for Clinical Chemistry (AACC) objected to the FDA emergency authorization of one self-collection test, describing the product as “unproven.”
Cue Health Nabs EUA
Cue Health has received emergency use authorization from the U.S. Food and Drug Administration (FDA) for its rapid, portable, point-of-care test for the novel coronavirus. The Cue Health COVID-19 molecular test detects SARS-CoV-2 nucleic acid from a nasal swab sample. It runs a 25-minute analysis directly at the point of care and delivers the results to the Cue mobile app. The test begins automatically when a nasal swab specimen is inserted into an accompanying Cue COVID-19 Test Cartridge, where heating, mixing, amplification, and detection all occur. The cartridge is connected to the Cue Health Monitoring System, which is in turn linked to an Apple iPhone device.
Cue’s single-use COVID-19 test kit includes the Cue COVID-19 Test Cartridge and sterile Cue Sample Wand. Users must have the Cue Health app installed on an iPhone model 8 or newer for the system to work.
The FDA emergency use authorization allows use of the CUE COVID-19 test at CLIA-certified labs that meet the requirements for high, moderate, or waived complexity tests. It also covers use at point-of-care sites that have a CLIA Certificate of Waiver. Cue hopes to expand the authorization for use in additional locations, such as schools, homes, and workplaces.
The test development received funding from the U.S. Biomedical Advanced Research and Development Authority. Cue is also currently developing additional test cartridges for its point-of-care system, including tests for influenza A and influenza B.
D-dimer Coagulation Test – Useful in COVID-19 Severity Assessment
Patients with COVID-19 who have high D-dimer levels are good candidates for CT pulmonary angiography (CTPA) to rule out acute pulmonary embolism (PE), according to a study published June 9 in European Radiology. The findings suggest a way clinicians can better evaluate the embolism risk in patients, since disease severity isn’t necessarily a significant measure, wrote a team led by Dr. Alban Gervaise of Military Hospital Begin in Saint-Mandé, France.
In fact, Gervaise and colleagues found that almost 20% of nonhospitalized patients with COVID-19 referred to CTPA by emergency department staff had acute pulmonary embolism — underscoring the importance of not making assumptions about patients with COVID-19 by the presenting acuity of the disease.
“Severity and radiological features of COVID-19 pneumonia showed no significant difference between patients with or without acute pulmonary embolism,” the team wrote.
Noncontrast chest CT — in conjunction with reverse transcription polymerase chain reaction (RT-PCR) testing — has been shown to be a useful tool for evaluating the pulmonary involvement of COVID-19, the authors wrote. CTPA’s use has been more limited, mostly in patients whose condition has worsened and in whom doctors want to check for acute pulmonary embolism.
Studies have confirmed a link between COVID-19 and acute pulmonary embolism in hospitalized patients with severe to critical illness, but it’s important not to assume that embolism is only present in this population, according to Gervaise and colleagues.
“In our practice, we have found cases of acute pulmonary embolism in nonhospitalized COVID-19 patients referred to CTPA by our emergency department,” they wrote.
The researchers sought to investigate the prevalence of acute pulmonary embolism in patients referred to CTPA by the emergency department. They conducted a retrospective study that included 72 patients who underwent CTPA between March 14 and April 6. Two radiologists evaluated the patients’ scans for acute pulmonary embolism; Gervaise’s team compared the clinical classification (minimal, moderate, severe, critical), lung involvement, and CT total severity score of patients with embolism and those without.
Of the 72 patients who underwent CTPA, 80% also had a positive RT-PCR test for SARS-CoV-2. CTPA identified embolism on 13 scans (18%). Of these, two had main, four had lobar, and seven had segmental acute pulmonary embolism. The most commonly affected lung segments were right lower lobe (61%) and left lower lobe (54%).
The investigators found that mean age and D-dimer values were higher in patients with embolism compared with those without, but they didn’t find a statistically significant difference between the two groups when it came to clinical type, lung lesions, CT severity scores, quality of the CTPA exam, or pleural effusion.
Abbott Releases Interim Study on IDNOW Accuracy vs. Other Tests in Urgent Care
In response to criticism about its IDNOW test, Abbott released an interim analysis of an ongoing multi-site clinical study in urgent care clinics that indicates its ID NOW COVID-19 rapid test is showing strong agreement to lab-based molecular polymerase chain reaction (PCR) instruments. The interim results are demonstrating ID NOW COVID-19 test performance is ≥94.7% in positive agreement (sensitivity) and ≥98.6% negative agreement (specificity) when compared to two different lab-based PCR reference methods.
Abbott answers criticism with a study showing IDNOW being used in the function the company says tests are supposed to be used, in active care with a sufficient symptom onset.
Data from this, as well as two other Abbott-sponsored studies – The Everett Clinic in Washington and an ongoing study of hospitalized and nursing home patients – suggest ID NOW performs best in patients tested earlier post symptom onset, when they are most likely to go for care. In these studies, ID NOW was used as intended with variations in patient populations based on the number of days a patient was tested after first experiencing symptoms.
The study found: In 256 subjects enrolled to date, ID NOW has identified 29 of 29 positive samples (100% positive agreement) and 226 of 227 negative samples (99.6% negative agreement) when compared to a commonly-used lab-based molecular PCR assay (the Roche cobas® SARS-CoV-2 assay). In parallel, ID NOW has demonstrated 94.7% positive agreement and 98.6% negative agreement compared to the Centers for Disease Control (CDC) 2019-Novel Coronavirus (COVID-19) Real-Time RT-PCR Diagnostic Panel. In comparison, Roche has demonstrated 95.0% positive agreement and 98.7% negative agreement when compared to the CDC assay. In these subjects, the mean number of days from symptom onset is 4.1 days with 90% of subjects tested within 7 days post symptom onset, when patients typically show up for care.
CDC Warns on Antibody Test Limits
The U.S. Centers for Disease Control and Surveillance (CDC) acknowledged high interest in antibody tests as businesses going back to work, while highlighting their limitations and many unknowns in reopening guidelines.
The agency published a 60-page documentwith guidelines for reopening, in accordance with White House plans, on its website. It includes instructions on testing, tracking, surveillance, and best practices for reopening daycares, schools, and businesses. During a May 20 White House briefing, press secretary Kayleigh McEnany downplayed the release, noting that several policies in the document had been previously published and that overall it represented an aggregation of guidelines on COVID-19.
Serology has been a hot button topic for reopening of economies in the U.S. and around the world. There has been talk of the potential for getting an immunity passport — evidence that one has been exposed to the novel coronavirus and has antibodies against it — as a means to regain entry to communal work environments, but test limitations get in the way. Laboratory medicine organizations have repeatedly flagged the risk for false positives.
In its guidelines for reopening, the CDC wrote that serologic testing “may play a role in a back-to-work strategy provided it can be shown that serologic testing can reliably infer immunity.”
AI-driven app uses blood biomarkers to flag high-risk COVID-19 patients
From Lab Pulse June 3, 2020 — A new mobile app uses artificial intelligence (AI) to assess key biomarkers from blood tests and help clinicians identify patients who are most at-risk for developing more severe cases of COVID-19.
- C-reactive protein (CRP)
- Myoglobin (MYO)
- Procalcitonin (PCT)
- Cardiac troponin I (cTnI)
These biomarkers can signal complications, like acute inflammation, lower respiratory tract infection, and poor cardiovascular health. Researchers built a model using the biomarkers and risk factors, like age and sex, and trained a machine learning algorithm to define the patterns of COVID-19 disease and give patients a severity score. After biomarkers and risk factors are entered into the model, it produces a score from 0 (mild or moderate) to 100 (critical).
Quidel Gets Direct w/ New Extractionless Test
Quidel earns an EUA for its Lyra Direct SARS-CoV-2 Assay. The test is a real-time RT-PCR assay intended for the in vitro qualitative detection of human coronavirus SARS-CoV-2 from viral RNA extracted from nasal, nasopharyngeal (NP) or oropharyngeal (OP) swab specimens from patients with signs and symptoms of COVID-19. Unlike most other systems, it does not require RNA extraction and instead uses a heating procedure. This new product means laboratories can work around supply shortages with extraction kits.
Update on Malaysia and COVID-19 Testing
This update is from AcuBiz, a Kuala Lumpur, Malaysia-based consulting services firm: https://acubiz.com.my/battling-covid-19-malaysia-making-steady-progress-with-ivds/
The Malaysian government took quick and effective steps to control large scale gatherings in the country, especially after new infections were traced back to a religious event in February, which was attended by over 15,000 people. With limited knowledge about the new enemy that the country needs to confront, the government acted fast taking effective measures to control the infection from spreading.
IVD companies in ASEAN, which responded to COVID-19 pandemic by launching multiplex RT-PCR tests include Mediven, ADT Biotech, and JN Medsys.
As the country was not equipped to do the required number of tests, social distancing was the immediate choice available for the government. The movement control order (MCO), which became effective on March 18, 2020, played a critical role in containing the spread of the pandemic and saving lives, as the chart below illustrates.
On May 4th, 2020, OECD published a report titled “Testing for Covid-19: A way to lift confinement restrictions”. The report highlighted the role of in vitro diagnostic (IVD) tests as countries worldwide are slowly relaxing the stringent measures taken for implementing social distancing as a measure to control the pandemic. The best exit strategy being recommended is testing, tracking, and tracing (TTT).
The OECD report defines three goals while developing testing strategies as suppressing the resurgence of local outbreaks, identifying people with immunity, and gaining intelligence on the evolution of the epidemic including identifying the threshold for herd immunity. For all the three goals, effective strategies for use of IVDs – molecular as well as serologic tests – are discussed.
Antigen rapid tests have also been approved by the MOH for screening. Malaysia has recently procured 200,000 antigen rapid tests from South Korea-based SD Biosensor, branded as Standard Q Covid-19 Ag. These tests have an accuracy of 84.4% and specificity of 100%. Though not as accurate as PCR tests, these tests offer a cost-effective option for large-scale testing.
Everlywell Home Test Collection Gets EUA
Everlywell announced that the company has received an Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for a COVID-19 at-home collection kit. Everlywell’s EUA is the first to be issued to a digital health company such as Everlywell, which is not a laboratory or diagnostics manufacturer. It is also the only EUA for at-home collection COVID-19 testing that is not tied to one specific lab and allows the company to work with a number of certified labs offering several authorized tests, rather than being limited to a single laboratory or a single test.
The at-home sample collection kit authorized by this EUA enables individuals to obtain a molecular PCR test designed to diagnose the presence or absence of the virus that causes COVID-19 through one of the company’s FDA-authorized laboratory partners. The company will use at least two CLIA-certified high-complexity partner laboratories to process tests at launch, with the intention of adding more laboratory partners as they receive authorization from the FDA for tests using Everlywell’s at-home sample collection kit. As with the company’s COVID-19 test offering for healthcare providers and organizations, this test kit will also be offered at no profit to Everlywell. The company says its $109 price will cover its costs, such as overnight shipping to the lab, lab processing fees, physician review and diagnosis, and kit components.
CDC flags shortcomings of antibody tests in reopening guidelines
The U.S. Centers for Disease Control and Prevention (CDC) acknowledged high interest in antibody tests as businesses go back to work, while highlighting their limitations and many unknowns in reopening guidelines.
The agency published a 60-page document with guidelines for reopening, in accordance with White House plans, on its website. It includes instructions on testing, tracking, surveillance, and best practices for reopening daycares, schools, and businesses. During a May 20 White House briefing, press secretary Kayleigh McEnany downplayed the release, noting that several policies in the document had been previously published and that overall it represented an aggregation of guidelines on COVID-19.
Serology has been a hot-button topic for the reopening of economies in the U.S. and around the world. There has been talk of the potential for getting an immunity passport — evidence that one has been exposed to the novel coronavirus and has antibodies against it — as a means to regain entry to communal work environments, but test limitations get in the way. Laboratory medicine organizations have repeatedly flagged the risk for false positives.
In its guidelines for reopening, the CDC wrote that serologic testing “may play a role in a back-to-work strategy provided it can be shown that serologic testing can reliably infer immunity.”
But the agency went on to say that despite public optimism about serologic testing to allow a return to work without the need for personal protective equipment (PPE) and other precautions, “there are many unknowns” that limit use for this purpose. For example, it’s unclear how antibodies correlate with immunity and there are concerns about accuracy.
“Typically, a well-performing single-step serologic assay may be expected to have a specificity of 95% (sensitivity is a secondary concern here, although also important), which is likely not enough for this purpose, given the potential consequences of COVID-19,” the CDC wrote. “Combining two different tests will be critical for improving performance and should be part of any strategy to utilize serologic testing for ‘immunity’ determinations.”
Furthermore, performance characteristics are still not known and seroprevalence has been shown to be “highly variable” even within different parts of the same city. If a test with 95% specificity was used in a population with true seroprevalence of 5%, almost half of the positive results would be false, the agency noted.
“At best, the use of serologic testing for a back-to-work strategy would likely benefit fewer than 10% of the population currently,” the document concluded.
The CDC called for a political consensus on top of scientific data to define the role of serological testing as part of business reopening plans.
“Consensus is also needed on a plan for how to provide documentation of that immunity, be it through federal- or state-based immunity registries, digital proof-of-immunity, or physical documentation such as ‘immunity certificates,’ ” the document stated.
In light of the interest in antibody testing, the CDC is working with other government agencies to evaluate assays, while tracking seroprevalence nationally.
Labs Feel the Pinch of Non-COVID-19 Testing Declines
Hospital and Reference Labs are feeling the pinch from the drops in elective surgeries, according to a survey conducted by Kalorama information. The results were unveiled at a webinar held by Kalorama and The Science and Medicine Group https://vimeo.com/413645455?utm_source=email&utm_medium=vimeo-cliptranscode-201504&utm_campaign=28749
Among the results:
- Chemistry testing (BMPs, electrolytes, etc) was reported down 19% in volume. Immunoassays down 21%.
- Histology testing is down 32%
- Molecular Testing volumes were up 8%
- PCT testing was the only other positive test category, up 2%.
- Blood Gas testing was down only 5%, cardiac troponin down 10%
- Labs expect to start to use more advanced molecular mass spec and NGS in 2020 and expect to increase chemistry and immunoassay testing as re-openings occur and hospitals reschedule surgeries.
- Layoffs were a factor at over one half of laboratories surveyed.
Biomerieux Test Designed to Outpace COVID-19 Mutations,
Biomerieux received EUA for its R-GENE COVID-19 test, a 2-test triplex gene assay that tests for multiple parts of the genome. The test is designed to guard against any mutations in the SARS-CoV-2. Most tests detect the N “spike” protein and one other area common to coronaviruses to determine a positive. The R-GENE tests runs for four RNA areas and 2 controls in two separate test runs.
Inside a NY Lab at the Epicenter
An article in longtime lab management publication Dark Daily explains how Northwell Health Laboratories, located on Long Island, is dealing with the crisis. The lab used a mobile team of phlebotomists to test residents at home, set up drive-thru tests and used GenMark and Hologic tests early on to boost testing volume and accuracy. They ramped up their capacity 30x in 14 days, made early calls on the use of nasal swabs to preserve supply, and used data to identify a problem with blood culture ordering. More here: https://www.darkintelligencegroup.com/the-dark-report/laboratory-management/at-the-epicenter-northwells-covid-19-lab-data-adds-value-2/
Swabs have become an issue, holding up testing because of a lack of supply. But why would there not be supply for so common an instrument? One reason is that there are two suppliers, Puritan Medical Products in Maine and Copan Diagnostics in Italy. Copan is in the center of its country’s own COVID-19 crisis which is causing additional supply delays. Former FDA Commissioner Scott Gottlieb, MD had warned on twitter mid-March that “ The weak link in supply chains are often low margin products, where there’s consolidated suppliers and relative under-investment — precisely because the products are lower margin and therefore don’t attract investment capital. Swabs could be a weak link in broadening testing.” There are some signs of progress from both companies. Puritan said the company was “…ramping up to produce and wrap a million swabs a week that we need to put into the supply chain across the U.S.” (https://www.bloomberg.com/features/2020-coronavirus-puritan-medical-test-swab.) Copan continues to deliver and on March 20th Air Force personnel loaded 13 pallets containing 500,000 COVID-19 testing swabs onto a C-17 Globemaster III cargo aircraft at Aviano Air Base in Italy.
Midturbinate Swab Options? There has been much coverage of the uncomfortable nasopharyngeal swab and awkward sampling procedure. A common industry refrain is that “you only get one nasopharyngeal swab from a child, you’ll never get one again.” Adults have been experiencing the same discomfort now given the crisis and it’s a popular test location for no one. In addition to discomfort, it is somewhat harder to perform and an error can lead to a mistaken test result, and exposes the test operator for a slightly longer period. By contrast, midturbinate swab specimens provide amore comfortable sampling experience. The midturbinate reason is halfway between the nasal and the nasopharyngeal area and forms the medial wall of the ethmoid sinus. And in studies of flu tests, there was only a small sacrifice in sensitivity at least in influenza. The CDCs revised guidelines allow them -“Nasopharyngeal swab is preferred, but if this is not possible, an oropharyngeal specimen, nasal mid-turbinate swab or anterior nares specimen will suffice” A recent study of four hundred eighty-four subjects with nasal, nasopharyngeal and midturbinate swabs obtained for each subject; 14% were children. Showed that the sensitivity for detecting influenza was 98% (95% CI 94.25% to 99.65%) with the midturbinate swab versus 84.4% (95% CI 77.5% to 89.8%) with the nasal swab, difference 13.6% (95% CI 8.2% to 19.3%). Specificity was 98.5% (95% CI 96.6% to 99.5%) with the midturbinate swab versus 99.1% (95% CI 97.4% to 99.8%) with the nasal swab, difference −0.6% (95% CI −1.8% to 0.6%). Swab discomfort levels correlated with the depth of the swab type. Median discomfort scores for the nasal swab, midturbinate swab, and nasopharyngeal swab were 0, 1, and 3, respectively. The tradeoff well worth it. https://www.copanusa.com/swab-flu-season-copan-contour-floqswab-stoppe
Large and Capable Molecular Diagnostics Industry Meets the Challenge
It’s worthwhile to consider that one of the first tasks of DNA-based when they arrived on the scene was the AIDS threat. The recent production of innovative assays by molecular diagnostics companies demonstrates the industries ability to respond to a new threat, as they had with HIV, Ebola, Zika, West Nile and others. The molecular diagnostics industry has large and well-financed companies such as Roche, Danaher, BD, Abbott, bioMerieux, Qiagen and Hologic. We noted last year that the molecular diagnostics market is larger than the economies of many countries. For instance, the market exceeds the individual GDPs of the Kyrgyz Republic at 8 billion or Fiji at $5 billion, or the smallest independent GDP in the world, the tiny 9-island nation of Tuvalu at $48 millions. More molecular diagnostic instruments and reagents will be sold this year than the GDP of Bermuda, Kosovo, and Sierra Leone, as well as those of 44 other nations, RT-PCR is the gold standard for virus detection and has taken center stage in the crisis. 30+ tests have received FDA EUA at this time.