There has never been so much concerted global focus on IVDs. And with good reason, as diagnostic testing has always proved essential to detect infectious disease threats and steer treatment and resources. We will assemble and update information here related to COVID-19 diagnostic testing. For more info, our complete guide to the IVD market, Worldwide Market for In Vitro Diagnostics is now in its 12th Edition.
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 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 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.”
Quidel Gets Direct
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.
Abbott EUA for high-throughput Alinity m is 5th for Company
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, Roche Serology Gets Nod, Siemens Healthineers Gets CE Mark. Rheonix, Euroimmun and Bio-Rad Nab FDA EUAs
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.
Roche announced that the U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA)1 for its new Elecsys® Anti-SARS-CoV-2 antibody test. The test is designed to help determine if a patient has been exposed to the SARS-CoV-2 virus and if the patient has developed antibodies against SARS-CoV-2. Roche has already started shipping the new antibody test to leading laboratories globally and will ramp up production capacity to high double-digit millions per month to serve healthcare systems in countries accepting the CE mark2 as well as the U.S. The serology test has a specificity greater than 99.8% and sensitivity of 100% Siemens Healthineers received the CE mark for its molecular Fast Track Diagnostics (FTD) SARS-CoV-2 Assay, allowing for its use as a clinical diagnostic test in Europe. The company says it will ship more than 1.3 million tests per month worldwide in May. The company will also develop an antibody test to detect IgM and IgG antibodies for detecting possible SARS-Cov-2 in the population.
Also the following companies received FDA emergency authorizations:
- LabGenomics Co., Ltd. EUA for “LabGun” COVID-19 RT-PCR Kit Molecular
- Rheonix, Inc. -EUA for Rheonix COVID-19 MDx Assay Molecular
- Bio-Rad Laboratories – EUA for Platelia SARS-CoV-2 Total Ab assay
- SEASUN BIOMATERIALS EUA for U-TOP COVID-19 Detection Kit Molecular
- Altona Diagnostics – EUA for its RealStar SARS-CoV02 RT-PCR Kits
Korean Testmakers SD Biosensor and Seegene Earn US EUAs
EUAs for RT PCR Kits Continue. Hamburg, Germany’s Altona Diagnostics received an EUA for its RealStar SARS-CoV02 RT-PCR Kits U.S. SD Biosensor also received a COVID-19 EUA. Seegene received an EUA for its Allplex™ 2019-nCoV Assay, a multiplex Real-time PCR assay for simultaneous detection of 3 target genes of SARS-CoV-2 in a single tube. The assay is designed to detect RdRP and N genes specific for SARS-CoV-2, and E gene for all of Sarbecovirus including SARS-CoV-2. The company claims the test provides results within 1 hour and 50 minutes after extraction.
Hospital Test Capacity Insufficient, Database Search Finds
Kalorama’s Clinical Masterfile reveals that capacity is not where it needs to be for many states to re-open. We called and identified 1300+ CLIA labs that do molecular testing – mostly located at US hospitals – with 2728 instruments that have the throughput capacity to run just under 1,000,0000 tests per day. This chart compares and ranks the states capacity versus the population, age risk, and population density. Assumptions are each site runs all known instruments continuously (3 shifts) with no shortage of reagents or kits. The Masterfile, produced by IMV (www.imvinfo.com) does not include reference labs, but given recent statements from high-profile companies about backlogs supply issues and layoffs, it is probable even with those sources added in, capacity is still a small percent of population.
Click here To obtain a license of our Kalorama Clinical Diagnostics Masterfile of 43,000 instruments and their locations at 5300 CLIA labs.
Blood gas lab testing one of a few winners, amid sagging volumes overall
The damage that COVID-19 causes in patients requires a number of medical interventions, assisted by a number of different diagnostics. While there is much focus on reverse transcription polymerase chain reaction (RT-PCR) tests for detecting SARS-CoV-2 infection in patients or in the population, once a patient is at the hospital, other tests come into play.
Thus, it should be no surprise that reports from test vendors and indications from Kalorama Information’s recent tracker survey of laboratories point to blood gas testing as one of the few test category “winners” amid sagging test volumes generally. Hospital end users reported increased volume recently. Because blood gas is also used in trauma and surgeries, and those have declined due to nationwide surgery cancellations and fewer emergency room visits, even a slight uptick in volume is notable.
In critical care medicine, blood gas analysis is combined with other critical care analytes including bilirubin for neonates, glucose, blood urea nitrogen (BUN), creatinine, calcium, ionized calcium, magnesium, lactate, pH, hemoglobin, and hematocrit. Blood gases, oximetry, and a cardiac marker panel are added for patients with chest pain. The most advanced critical care test devices include various cartridge combinations of gases, electrolytes, and others depending on the patient care situation. These may be used for point-of-care testing in intensive care units, emergency rooms, ambulances, and other acute care venues as well as in laboratories.
Radiometer is a leading company in blood gas testing. The company’s ABL800 Flex blood gas analyzer offers high throughput and automated sample handling — what the company calls “Drop ‘n’ Go” capability. The operator does not need to wait at the analyzer for results.
Siemens Healthineers recently announced that its latest critical care testing solution — the RapidPoint 500e blood gas analyzer — has received clearance from the U.S. Food and Drug Administration (FDA), and is now available in the U.S., Europe, and countries requiring the CE Mark. The analyzer generates blood gas, electrolyte, metabolite, CO-oximetry, and neonatal bilirubin results, which are used to diagnose and monitor critically ill patients in the intensive care unit, operating room, or emergency room.
Instrumentation Laboratory’s Gem Premier 5000 is a competitive blood gas testing system that provides automated quality assurance with every sample. The Premier 500’s integrated iQM2 with IntraSpect offers automated quality assurance with every sample, continuously and in real-time. Error detection time is reduced from hours to minutes and errors are automatically corrected and documented for a complete picture of quality.
Other competitors include Roche Diagnostics’ cobas b 123 point-of-care system and Nova Biomedical’s StatProfile pHOx Ultra. Roche’s system provides throughput of up to 30 samples per hour. Nova Biomedical’s test boasts 20 critical care tests from a 210-µL sample in two minutes.
Abbott has the leading handheld product in critical care. The lightweight i-Stat 1 blood analyzer uses single-use i-Stat test cartridges for critical care tests. The product has gained significant market share with a continuous menu expansion to include basic chemistries, blood gases, electrolytes, coagulation, hematology, and cardiac markers. Abbott has reported that more than 50,000 i-Stat handhelds are used by healthcare professionals in a variety of high-acuity settings worldwide — including in more than 1,800 hospitals. More than 50 million test cartridges are produced annually. The company’s “CG4+” cartridge can also add sepsis determination, determining the presence of hyperlactatemia to inform the risk stratification of patients diagnosed with sepsis.
i-Stat is popular, but it is not the only handheld system. Siemens Healthineers’ Epoc is a competing handheld wireless solution to enable comprehensive blood analysis testing at the patient’s side on a single room temperature test card, with results in less than a minute. Radiometer’s ABL80 Flex blood gas analyzer is a small, portable version for low-volume settings. The system uses battery power. Other handheld devices are marketed by Opti Medical and LifeHealth.
Though it is a mature test category, blood gas test technology has changed over time. Information technology innovations have improved performance and interpretation in blood gas testing. Roche announced CE Mark availability of Roche v-TAC, a new digital software that allows clinicians to obtain results for arterial blood gas values through the use of a digital algorithm. Instrumentation Laboratory added “custom connectivity” to its systems recently, featuring an at-a-glance dashboard, and simple web access from any browser, with remote control of analyzer configuration and the ability to monitor critical care operators from a central location, according to the company.
FDA to Review Antibody Tests
The FDA has clarified its policy on antibody tests. “All clinical tests should be validated prior to use, and this expectation is articulated in our March 16 policy,” the agency said in a recent statement. Though tests may be marketed prior to review, the agency must be notified and appropriate warnings must be given. Tests must be validated and the FDA will review validation of these tests. “We have provided regulatory flexibility regarding the independent check by FDA for antibody tests that are limited in their clinical applications, but still expect all developers to validate their tests prior to offering them for limited clinical uses. To minimize the number of false positive results, serological tests must be well-designed to specifically identify antibodies against SARS-CoV-2 and must not “cross-react,” or provide positive results when encountering antibodies against other respiratory viruses.” They will act on tests that do not perform, state that they are FDA approved when they are not, claim they are for diagnosis, or for which there is no notification to the FDA.
100+ Antibody Test Vendors Notified FDA
100 firms had notified the FDA. https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-diagnostic-testing-sars-cov-2
ACLA Asks for Improved Reimbursement of COVID-19 Serology Tests
The American Clinical Lab Association (ACLA) says that the way molecular testing was reimbursed cannot be repeated with serology testing. The organization issued a statement asking for improved reimbursement of serology tests based on the experience with molecular testing:
First Antibody Test Not Reaching U.S. Yet
Cellex broke news of the first EUA for an antibody test, but tens of thousands of test kits remain in China. This news comes as antibody testing is in demand and as more established U.S. players Chembio and OrthoClinical have now also received EUAs. “The Chinese government issued an export restriction on COVID-19-related medical products,” Cellex said in a statement. “While it may have good intention, it nonetheless prevented our test from being shipped out of our production, per ABC News – https://abcnews.go.com/International/crucial-coronavirus-antibody-tests-destined-york-city-caught/story?id=70199489
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.
BD Max Test in Hundreds of Hospital Labs
BD (Becton Dickinson and Company) and BioGX have received the US Food and Drug Administration’s (FDA) emergency use authorisation (EUA) for a new coronavirus (Covid-19) test. The new diagnostic test enables hospitals to screen for Covid-19 onsite and receive results within three hours. It is run on the BD MAX System and is capable of analysing hundreds of samples a day. https://www.medicaldevice-network.com/news/bd-biogx-emergency-use-authorisation-covid-19-test/
BD and BioMedomics, a privately held, North Carolina-based clinical diagnostics company, today announced the release of a new point-of-care test that can detect antibodies in blood to confirm current or past exposure to COVID-19 in as little as 15 minutes. https://www.bd.com/en-us/company/news-and-media/press-releases/bd-biomedomics-announce-launch-of-rapid-serology-test-to-detect-exposure-to-covid-19
C.D.C. Issues Return to Work Guidelines for Essential Workers
The Centers for Disease Control and Prevention published new guidelines on Wednesday detailing how essential employees can go back to work even if they have been exposed to people infected by the coronavirus, provided they do not feel sick and follow certain precautions. Those employees can return if they take their temperature before heading to their workplaces, wear a face mask at all times and practice social distancing. Employers should send workers home immediately if they developed any symptoms. He also said they should increase air exchange in their buildings and clean common surfaces more often. The goal, he said, was to “get these workers back into the critical work force so that we don’t have worker shortages.” Air Exchange: Among these suggestions is better air exchange at workplaces: Air exchange is, per https://www.airassurance.com/blog/2018/04/26/air-exchange-rate “the number of times that air gets replaced in each room every hour. The American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) provides guidelines for air changes per hour, and they vary depending on the room: bedrooms should have five–six, kitchens 7–8, and laundry rooms require 8–9 changes.” According to a recent study studying air exchange and flu virus: (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123350/) “There is mounting evidence that the aerosol transmission route plays a significant role in the spread of influenza in temperate regions and that the efficiency of this route depends on humidity.” According to the American Lung Association: When someone sneezes or coughs, tiny water or mucous droplets filled with viruses or bacteria scatter in the air or end up in the hands where they spread on surfaces like doorknobs. Inhaling these viruses or bacteria can spread coughs, colds, influenza, tuberculosis and other infectious agents. Crowded conditions with poor air circulation can promote this spread. Some bacteria and viruses thrive and circulate through poorly maintained building ventilation systems, as with Legionnaires’ disease. Damp, humid air can increase the survival rate of viruses indoors.
Some Discussion of How and When COVID-19 Came to the United States
https://www.nytimes.com/2020/04/08/us/coronavirus-live-updates.html Of the NY COVID-19 cases, “The majority is clearly European,” said a New York Times article, quoting Harm van Bakel, a geneticist at Icahn School of Medicine at Mount Sinai, who co-wrote a study awaiting peer review while A separate team at N.Y.U. Grossman School of Medicine agreed in a study of a different group of cases. ‘Both teams analyzed genomes from coronaviruses taken from New Yorkers starting in mid-March,” the article said. Meanwhile – a Stanford professor believes the virus came searlier than reported and has possibly built herd immunity, explaining California’s better outcome so far despite a large population.. https://www.ksbw.com/article/new-study-investigates-californias-possible-herd-immunity-to-covid-19/