August 7, 2020 | In a report in the Journal of Molecular Diagnostics, researchers describe a cheaper, rapid, and accurate pooling strategy for the RT-PCR-based detection of SARS-CoV-2 in clinical samples. Elsewhere, the U.S. Food and Drug Administration has authorized the first two COVID-19 serology tests that display an estimated quantity of antibodies present in the individual’s blood. This, plus more, is included in this week’s COVID-19 news and research in the diagnostics industry.
Literature Updates
Patients with COVID-19 presenting with acute neurologic symptoms warrant a lower threshold for suspicion of large vessel occlusion (LVO) stroke, thus necessitating prompt workup, according to a retrospective, case-control study by Mount Sinai researchers that published in the American Journal of Roentgenology. The study included 329 patients for whom a code for stroke was activated during March 16 to April 30, 2020 at a single system of six hospitals in New York City; for 21.6% is was determined to be a LVO stroke, the most common type being middle cerebral artery segment M1-M2 occlusion. Multifocal LVOs were observed in only 9.9% of patients with LVO stroke. LVO stroke was present in 31.7% of patients with COVID-19, compared with 15.3% of patients without COVID-19. The figures were 1.9% and 13.8%, respectively, for SVO stroke. DOI: 10.2214/AJR.20.23847
Researchers from Children's Hospital of Philadelphia have identified lab profiles that differentiate Multisystem Inflammatory Syndrome in Children (MIS-C) from severe COVID-19 in children and suggest that MIS-C is a post-infectious syndrome that is distinct from Kawasaki disease (KD). Their findings published in The Journal of Clinical Investigation. The study analyzed 20 patients with SARS-CoV-2 and found that patients with MIS-C had elevated levels of two cytokines—IL-10 and TNF-α—whereas patients with severe or mild COVID-19 had no or minimally elevated levels of these cytokines. In previous reports, KD profiles tend to be associated with mild elevations of other cytokines and not IL-10. An additional finding was that severe COVID-19 is easily detectable and active, while patients with MIS-C had been infected with the virus at some point in the distant past and cleared most of the active virus. Simple peripheral blood smears could also help distinguish severe COVID-19, mild COVID-19 and MIS-c. DOI: 10.1172/JCI140970
In a report in the Journal of Molecular Diagnostics, researchers at Augusta University and PerkinElmer Genomics describe a cheaper, rapid, and accurate pooling strategy for the RT-PCR-based detection of SARS-CoV-2 in clinical samples. The assay could have a significant impact on large-scale population screening in the wake of the current COVID-19 pandemic, leading to a five- to 10-fold reduction in the cost of SARS-CoV-2 testing. Investigators analyzed approximately 1,000 samples using this pooled sampling approach and achieved 91.6% positive percent agreement and 100% negative percent agreement compared to the routine screening approach. They say one million individuals can be tested for around $9.1 million with the proposed mass population screening approach compared to about $58 million with current routine diagnostic methods. DOI: 10.1016/j.jmoldx.2020.07.001
A Swiss-German research team has launched a SARS CoV-2 antibody test that takes only 18 hours and doesn't have high biosafety requirements. A traditional neutralization test usually takes two to three days and must be carried out with infectious coronaviruses in a laboratory complying to biosafety level 3. The new test is described in a recent report in Vaccines. The authors explain that they exchanged the envelope protein of a virus that doesn't propagate for the spike protein of the novel coronavirus, which mediates virus entry and infection. As a result, the viruses can be identified by antibodies against SARS-CoV-2. The antibodies bind to the altered viruses and neutralize them so they can no longer penetrate the host cells. Since the virus “pseudo-typed” in this way can't propagate in host cells, no elaborate biosafety precautions are necessary for the test. DOI: 10.3390/vaccines8030386
A study authored by representatives of Quest Diagnostics has found a significant decline in newly identified patients in the U.S. with six common types of cancer before and during the COVID-19 pandemic, mirroring findings from other countries. The study included 278,778 patients, 92.8% from the baseline period (Jan. 6, 2019 to Feb. 29, 2020) and the remainder from the COVID-19 period (March 1 to April 18, 2020). During the pandemic, the weekly number of newly identified patients fell 46.4% overall, with significant declines in all cancer types—ranging from 24.7% for pancreatic cancer to 51.8% for breast cancer. Results published in JAMA Open Network. DOI: 10.1001/jamanetworkopen.2020.17267
The death rate for patients who experienced what is normally a lower-risk heart attack rose sharply during the peak of the COVID-19 pandemic in England, according to an analysis of NHS data published in the European Heart Journal - Quality of Care and Clinical Outcomes. In comparison, the death rate for people who had a more severe heart attack fell. It also revealed a substantial drop in the number of people who were arriving at hospital with a heart attack. At its lowest point, hospitals were treating just over half the cases they would normally expect to see. The number of people seeking medical help still had not returned to pre COVID-19 levels when the study period ended on May 22. The reduction in patients seeking timely help is likely to have resulted in people dying at home or developing chronic heart problems, report the research team, led by the University of Leeds. DOI: 10.1093/ehjqcco/qcaa062
In a letter published in JAMA Dermatology, researchers at NewYork-Presbyterian/Weill Cornell Medical College report that livedoid and purpuric skin eruptions are associated with coagulopathy in severe COVID-19. If these skin findings are identified, they advise taking a skin biopsy as it may guide anticoagulation management. Even in the absence of other thrombotic events, they say, consultation with hematology staff and escalation of anticoagulation should be considered. DOI: 10.1001/jamadermatol.2020.2800
A large proportion of U.K. healthcare workers may already have been infected with COVID-19, according to research led by the University of East Anglia in collaboration with University College London. Findings were based on a questionnaire completed by 262 healthcare workers in April, before anosmia was listed as an official symptom and diagnostic testing among NHS workers was limited to those displaying symptoms of a new continuous cough and/or a high temperature. Nevertheless, 27.9% of the participants had been tested for COVID-19, with 76.7% of these confirmed positive. Interestingly, nearly two-thirds of those surveyed reported that they had lost their sense of smell or taste at some point between mid-February and mid-April, as reported in The Lancet Microbe. Those who had lost their sense of smell were also almost five times more likely to test positive. The study also involved a follow-up survey in May, in which 47% of respondents reported that their sense of smell and taste had completely recovered. A further 42% said they had partially recovered their sense of smell and taste, but just over 7% still suffered anosmia. DOI: 10.1016/j.wjorl.2020.04.001
Researchers in Korea have determined that the viral load of asymptomatic and symptomatic patients is similar, and that the cycle threshold values of envelope genes from lower respiratory tract specimens (sputum) in asymptomatic patients tended to decrease more gradually than those of symptomatic patients. Symptom-based surveillance and screening methods may result in substantial under-reporting of infected patients, they say, noting a report of SARS-CoV-2 transmission from an asymptomatic person to four family members that offers biological plausibility to the infectiveness of asymptomatic people. The retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center. Results appeared in JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2020.3862
When people seek emergency care for shortness of breath, a routine electrocardiogram (ECG) enhanced by artificial intelligence (AI) is better than standard blood tests at determining if the cause is heart failure, according to Mayo Clinic researchers in a study published in Circulation: Arrhythmia and Electrophysiology. To create the AI-enhanced ECG, they used data on thousands of patients to train computers to distinguish between the ECG patterns of people ultimately diagnosed with left ventricular systolic dysfunction (LVSD) and those without LVSD. In about 10 seconds, standard ECG recordings can be analyzed with the resulting AI software application to identify likely LVSD. When AI enhancement was applied to the ECGs of 1,606 patients, it outperformed standard blood tests in identifying which patients have severe LVSD, did a good job of identifying patients with less severe but abnormally low pumping ability and performed just as well in men and women and among patients in different age groups. In May, the FDA granted emergency use authorization of the AI-enhanced ECG algorithm to screen for LVSD in people with confirmed or suspected COVID-19 disease. DOI: 10.1161/CIRCEP.120.008437
Industry Updates
The U.S. Food and Drug Administration has authorized the first two COVID-19 serology tests that display an estimated quantity of antibodies present in the individual’s blood. Both tests from Siemens, the ADVIA Centaur COV2G and Atellica IM COV2G, are what are known as “semi-quantitative” tests, meaning that they do not display a precise measurement, but estimate the quantity of a patient’s antibodies produced against infection with the virus that causes COVID-19. Press release.
Oxford Nanopore launched its novel LamPORE SARS-CoV-2 test and announced an agreement with the UK’s Department of Health and Social Care, to make an initial 450,000 LamPORE tests available for use by a number of NHS testing laboratories. As well as providing a large number of tests for existing labs, the program will help the UK to understand the different use cases for the technology, for example the potential asymptomatic screening of frontline staff. Because of its scalability, LamPORE has the potential to provide both large-scale screening to detect the virus in broader populations, and rapid, focused, localized analysis. LamPORE is designed to be deployed on Oxford Nanopore’s desktop device (GridION) or palm-sized device (MinION Mk1C), providing the capacity of processing up to 15,000 saliva or swab RNA samples a day or 2,000 samples a day respectively. It is well suited to use in a central laboratory for high-throughput sample processing, or near-community ‘pop-up lab’. LamPORE results can be generated in under two hours. Oxford Nanopore is currently also developing LamPORE to test for multiple pathogens within a single sample, including influenza A (H1N1 and H3N2), influenza B, respiratory syncytial virus (RSV) and SARS-CoV-2. This is intended to allow healthcare professionals to distinguish between these infections, better manage expected winter pressures on the NHS and guide public health and clinical management of these diseases at a time of traditionally heightened pressure on health services. Press release.
SOPHiA GENETICS has launched a multimodal solution to predict COVID-19 disease evolution and support containment efforts globally by demonstrating immediate benefits for community contact tracing and essential viral monitoring research. Detecting the disease and predicting its course and outcomes both continue to be major challenges for optimal COVID-19 management. There are a number of variables that can be linked to the likely disease evolution including viral strain, host genetic response factors, and clinical management of cases. SOPHiA GENETICS has built an AI-powered solution to conduct full-genome analysis of SARS-CoV-2. It can compare insights from the viral genomic data with human “host” genetic information. In addition, the new SOPHiA Radiomics for COVID-19 offers a CT-based automated workflow for whole-lung segmentation and disease quantification. With an easy to use interface, radiomic features are extracted from lung abnormalities and well-aerated areas. Our unique machine learning is applied to more easily discover abnormalities predictive of disease evolution and leverage multimodal research data sets. Press release.
Avacta Group, the developer of Affimer biotherapeutics and reagents, has appointed BBI Solutions to manufacture the saliva-based rapid SARS-CoV-2 antigen test that is being developed with Cytiva. The manufacturing agreement between Avacta and BBI comprises the accelerated development and validation of a scaled-up manufacturing process that has the potential to ramp up to a production capacity of millions of tests per month. Avacta, Cytiva, and BBI are in the process of the technology transfer of the prototype and related manufacturing procedures for the saliva-based rapid SARS-CoV-2 antigen test from Cytiva to BBI. Press release.
Mammoth Biosciences has received a contract from the National Institutes of Health (NIH) as part of its $1.5 billion Rapid Acceleration of Diagnostics (RADx) program. The award will help scale Mammoth Biosciences’ CRISPR-based DETECTR test onto high-throughput automated platforms in commercial labs for COVID-19 diagnostics at an accelerated rate, increasing access to accurate tests with faster turnaround across the country. In a move to double down on its diagnostics efforts, Mammoth Biosciences has also strategically hired three new additions to its leadership team, including Rachel Herder as Vice President of Intellectual Property (IP), Jesus Ching as Vice President of Research and Development, and Tim Patno as Vice President of Product Development. Press release.
Brainworks has launched Medio Smart Health, an AI-enhanced, non-contact vital sign measurement and automated digital healthcare tool for personal health management and COVID-19 specific symptom tracking. With Medio, individuals can use their mobile phones, computers, and tablet cameras to automatically measure and track their vital signs, monitor their health over time, and answer specific CDC recommended screening questions related to COVID-19. Specific, trackable symptoms related to COVID-19 detected through video-based ambient biometrics, including heart rate, respiration rate, and changes in skin tone related to blood oxygenation are automatically measured by the cameras in iOS Safari-enabled mobile devices as well as other smartphones, tablets, and PCs. The easy-to-use website is available for immediate use, allowing users to track changes to their health and determine whether they should seek additional testing, medical care, or hospitalization. Press release.
Accumen has announced a partnership with medical equipment manufacturer, Spectrum Solutions, to provide COVID-19 saliva testing kits nationally. Saliva testing for detecting COVID-19 first received FDA Emergency Use Authorization (EUA) in April. This authorization mandated saliva collection solely using Spectrum’s SDNA-1000 saliva collection device based on a trial with Rutgers University. The Spectrum saliva collection kit has been engineered to produce more accurate and sensitive test results, reduce sample collection errors—including for at-home self-collection—reduce labor required for collection and reduce use of valuable PPE. Additionally, the SDNA-1000 delivers 100% neutralization of the live virus mitigating risk and the threat of unnecessary exposure. It can also preserve and stabilize viral RNA transcripts for transport in extreme and varying temperatures for more than 14 days and for up to one-year post collection in ambient storage. Press release.
Chan Zuckerberg Biohub (CZ Biohub) in partnership with the Chan Zuckerberg Initiative (CZI), announced that it will provide free whole genome sequencing and analysis of the SARS-CoV-2 virus to all California Departments of Public Health (DPH) and California local health jurisdictions through a newly-launched effort called the California COVID Tracker. The aim of the initiative is to provide actionable viral genomic data to local public health jurisdictions and help ensure transmission remains low during the wait for a vaccine. CZ Biohub will provide sequencing, analysis, and interpretation support, with an emphasis on making data actionable for public health surveillance and response. This type of actionable genomic epidemiology program is not currently available anywhere else in the U.S. As part of the effort, CZ Biohub will deposit SARS-CoV-2 sequences into public repositories for COVID-19 genomics, including GISAID and NCBI. CZ Biohub and CZI will provide tools and analysis support to help California DPHs overlay epidemiological and demographic information onto this genomic data to better understand local SARS-CoV-2 transmission. Press release.
Scientists at the University of Pittsburgh and the University of Notre Dame are working to improve CT scan screening for COVID-19 by training a computer to analyze images and do the diagnostic heavy lifting. The potential of deep neural networks to identify typical or partial signs of COVID-19 pneumonia has recently been demonstrated, and the team’s goal is to train an algorithm to be able to tell the difference between regular pneumonia and the type of pneumonia caused by the novel coronavirus. Deep neural networks are not well equipped to handle the amount of data associated with 3D images, so various hardware and software solutions will be explored allowing the technology to adapt to these larger files. Press release.
The National Institutes of Health reports that the “shark tank” approach used by its Rapid Acceleration of Diagnostics (RADx) initiative is directing its investment in technologies that could boost America's best-in-the-world COVID-19 testing capacity by millions more tests per day as early as September 2020. The agency has awarded contracts to seven biomedical diagnostic companies using different testing methods and formats that can be performed in a variety of settings to meet diverse needs. Four of the technologies introduce innovations in laboratory-based testing technologies, including next generation sequencing, CRISPR and integrated microfluidic chips; three use platforms to provide nucleic acid and viral antigen tests that can give rapid results at the point of care; and some of the tests offer more convenient sampling, such as saliva testing. The companies that have achieved key RADx milestones and will receive support for manufacturing and scale up are Mesa Biotech (San Diego), Quidel (San Diego), Talis Biomedical (Menlo Park, California), Ginkgo Bioworks (Boston), Helix OpCo (San Mateo, California), Fluidigm (San Francisco) and Mammoth Biosciences, Inc. (South San Francisco, California). Press release.
Researchers at ICFO-The Institute of Photonic Sciences (Spain) used algorithms to customize a commercial, near-infrared spectroscopy device that will provide an evaluation of the microvascular health. After the first device was sent to Hospital Parc Taulí in March to be tested on COVID-19 patients, the collaboration expanded into an international consortium named HEMOCOVID-19 that is using the response of the microvasculature in the peripheral muscles to prolonged arterial cuff or blockage as a biomarker of endothelial and microvascular health. The device—non-invasive, portable, wireless and battery-operated—takes measurements at different times during patients’ intensive care stay. The goal is to help clinicians in the stratification of patients and guide development of therapies targeting the endothelial function as well as personalized rescue therapies that play a critical role in the management of severely ill patients. The consortium currently has 10 partners in Spain, the U.S., Brazil and Mexico. Press release.
The German Center for Infection Research is building a platform that will gather the methodology and results of SARS-CoV-2 antibody tests and make the data available to interested researchers. The project, called the LEOSS.sero-survey, will be led by scientists at the Helmholtz Centre for Infection Research and implemented in collaboration with Helmholtz Federated IT Services. The objective is to learn who has overcome COVID-19 without noticing and how many people have already produced protective antibodies against the virus. Seroprevalence studies are the only way to know the actual level of immunity in the population. LEOSS.ser-survey offers research groups the opportunity to collect and jointly evaluate the anonymized data of the various studies to increase their statistical significance. The platform follows the example of the existing LEOSS patient register, which has been collecting and evaluating clinical data from COVID-19 patients throughout Europe since March. With the LEOSS.sero-survey, the second important step being taken focuses on the immunity of affected people. Press release.
A new Medical Imaging and Data Resource Center (MIDRC) at the University of Chicago will create a massive, open-source database with medical images from thousands of COVID-19 patients to help better understand and treat the disease. The effort is being co-led by the American College of Radiology (ACR), the Radiological Society of North America (RSNA), and the American Association of Physicists in Medicine (AAPN), with funding coming from the National Institute of Biomedical Imaging and Bioengineering of the NIH. MIDRC will enable technological advancements, guide researchers' validation and use of artificial intelligence, and translate clinical systems for the best patient management decisions. Investigators will be able to access images and data to expedite their research through the MIDRC Data Commons Portal. The project will involve five infrastructure development projects under the oversight of an MIDRC executive advisory committee that will also oversee 12 research projects in support of solutions to the COVID-19 pandemic and the provision of funding and other resources to investigators at the ACR, RSNA, AAPM, 20 universities and the FDA. Within three months, the MIDRC plans to upload more than 10,000 COVID-19 thoracic radiographs and CT scan images via the existing input portals of the RSNA repository and the ACR registry. Press release.