September 18, 2020 | Differing nasal expressions in blacks, a risk stratification tool for athletes, a new antibody test for identifying plasma donors, warning for patients with sleep apnea, the utility of infrared thermographs, lower pulse oximetry levels and fever lead reasons for rehospitalizations, and a Lab-in-Cartridge device rolling out across the U.K. Plus, a dual-purpose nonprofit, computing how to allocate test kits, seven digital health solutions receive NIH funding, and efforts underway to standardize SARS-CoV-2 assays.
Research Updates
In JAMA Pediatrics, researchers in Italy report on a case-control study comparing the rate of test results indicating SARS-CoV-2 infection among children (about 1% among 881 individuals) and adults (9% among 3,610 individuals) admitted to a single hospital in Milan for noninfectious reasons and without COVID-19 symptoms between March 1 and April 30, 2020. The role of children as facilitators of the spreading of SARS-CoV-2 infection could be reconsidered, they conclude. DOI: 10.1001/jamapediatrics.2020.3595
Significantly higher nasal expression of transmembrane serine protease 2 (TMPRSS2) may partially contribute to COVID-19 risk among blacks, suggests a study by Mount Sinai researchers that published in JAMA. Blacks have experienced rates of infection and death that in some areas are twice or three times more than their proportion of the population. The retrospective analysis drew on a cross-sectional study of 305 patients of diverse racial/ethnic backgrounds, ages 4-60, within the Mount Sinai Health System, from whom nasal samples were collected. The critical importance of including diverse participants in clinical trials, particularly those of TMPRSS2 inhibitors, was one of the key takeaways of the findings. DOI: 10.1001/jama.2020.17386
Cardiac magnetic resonance (CMR) imaging may provide an excellent risk-stratification assessment for myocarditis in athletes who have recovered from COVID-19 to guide safe competitive sports participation, according to a study by researchers at The Ohio State University that appeared in JAMA Cardiology. CRM imaging was performed on 26 competitive college athletes between June and August 2020, suggesting four had myocarditis and another eight had prior myocardial injury. CMR mapping techniques have a high negative predictive value to rule out myocarditis, the authors note. DOI: 10.1001/jamacardio.2020.4916
A study published in The Journal of Clinical Investigation reports on an antibody test for SARS-CoV-2 that is more accurate and can handle a much larger number of donor samples at lower overall cost than standard antibody tests currently in use. The easy-to-perform ELISA test was developed by researchers at the University of Texas at Austin in collaboration with Houston Methodist, Penn State University and the U.S. Army Medical Research Institute of Infectious Diseases. The study used the assay to evaluate 2,814 blood samples from an ongoing study of convalescent plasma therapy and concluded that anti- receptor binding domain or anti-ectodomain antibody levels can serve as a surrogate for virus neutralizing levels to identify suitable plasma donors and that these alternate ELISA tests may provide critical information about COVID-19 immunity. In the near term, the test can be used to accurately identify the best donors for convalescent plasma therapy and measure how well candidate vaccines and other therapies elicit an immune response. Additional uses coming later that are likely to have the biggest societal impact, the researchers say, are to assess relative immunity in those previously infected by the SARS-CoV-2 virus and identify asymptomatic individuals with high levels of neutralizing antibodies against the virus. DOI: 10.1172/JCI141206
People who have been diagnosed with obstructive sleep apnea could be at increased risk of adverse outcomes from COVID-19, according to a study from the University of Warwick (U.K.) that published in Sleep Medicine Reviews. The conclusion was drawn from a systematic review of 18 studies published through June 2020 and highlights the need to further investigate the impact of the virus on those with the sleep condition and to better identify those currently undiagnosed with it. Eight of the referenced studies were mainly related to the risk of death from COVID-19 and 10 were related to diagnosis, treatment and management of sleep apnea. Although few studies of obstructive sleep apnea in COVID-19 had been performed at the time, there is evidence to suggest that many patients who presented to intensive care had obstructive sleep apnea and in diabetic patients it may confer an increased risk that is independent of other risk factors. In one large study in patients that had diabetes and were hospitalized for COVID-19, those being treated for obstructive sleep apnea were at 2.8 times greater risk of dying on the seventh day after hospital admission. Researchers believe that up to 85% of obstructive sleep apnea disorders in the U.K. are going undetected. DOI: 10.1016/j.smrv.2020.101382
Although the use of thermography as a stand-alone detection method for COVID-19 is unlikely to prevent spread, emerging evidence and international consensus suggest that it is possible to use infrared thermographs (IRTs) effectively for detecting elevated body temperatures—including low-grade fevers associated with early-stage infections and moderate symptoms. This is according to researchers from the FDA, the University of Maryland and John Hopkins University in a report published in the Journal of Biomedical Optics. They provide robust insights for optimizing IRT-based fever screening, based on research evaluating its use under standardized conditions. Clinical data was examined for more than 500 demographically diverse individuals, correlating facial temperatures to oral under-the-tongue thermometer measurements. The team confirmed the utility of internationally recognized (ISO) standards for obtaining consistently accurate results, and specifically reported the efficacy of ISO methods, including facial area targets. One of the most significant insights was that targeting the full face for temperature screening resulted in greater accuracy than narrowly targeting the inner canthi, as recommended by the ISO guidelines. Researchers also calculated a series of cutoff levels to optimize the sensitivity and specificity values of the IRT readings. For COVID-19 in particular, the FDA has published fact sheets on the proper use and limitations of these systems. DOI: 10.1117/1.JBO.25.9.097002
Roughly 1 in 10 patients diagnosed with COVID-19 needed to return to the hospital within a week of discharge from an emergency department (ED) visit, according to data from the first three months of the COVID-19 outbreak in the Philadelphia region. Researchers in the Perelman School of Medicine at the University of Pennsylvania also found that factors like lower pulse oximetry levels and fever were some of the most telling symptoms that resulted in return trips that resulted in admission. Other factors, such as an abnormal chest x-ray, further raised the risk of return and admission. The study looked at 1,419 patients who went to an ED between March 1 and May 28, 2020, were discharged, and tested positive for COVID-19 in the seven days surrounding that visit. Data showed that 4.7% of the patients returned to the hospital and were admitted within just three days of their initial ED visit, and an additional 3.9% were hospitalized within a week. Patients over 60 years old were particularly vulnerable. Findings published in Academic Emergency Medicine. DOI: 10.1111/acem.14117
Passive sentinel surveillance for COVID-19 in homeless shelters and other congregate living situations may only detect symptomatic cases while missing milder ones, according to a community-based surveillance study conducted by researchers at the University of Washington School of Medicine that published in the Annals of Internal Medicine. Active testing is needed to identify cases and potentially prevent outbreaks and further viral spread. Most of 29 COVID-19 cases at five homeless shelters were detected during one-day surge testing (contact tracing) events rather than routine surveillance and, of those, most were asymptomatic at the time of sample collection; 86% of persons with positive test results slept in a communal space rather than in a private or shared room. DOI: 10.7326/M20-3799
A 90-minute COVID-19 test has been shown to have over 94% sensitivity and 100% specificity in a new study, led by scientists from Imperial College London, which published in The Lancet Microbe. The tests, which can be performed in cartridges smaller than a mobile phone, were used on 386 National Health Service staff and patients. The Lab-in-Cartridge rapid testing device is currently being used across eight London hospitals and will be rolled out at a national level. The U.K. government recently placed an order for 5.8 million of the testing kits. To perform the test, a pediatric-sized nose swab from a patient is inserted into the device, which then looks for traces of genetic material belonging to the SARS-CoV-2 virus. The Wi-Fi-enabled device, produced by startup DnaNudge, is now being further developed to simultaneously assess for Flu-A, Flu-B, and RSV. DOI: 10.1016/S2666-5247(20)30121-X
Industry Updates
Sherlock Biosciences has announced the creation of The 221b Foundation to address the global COVID-19 pandemic by enabling access to intellectual property associated with the company’s Specific High Sensitivity Enzymatic Reporter unLOCKing (SHERLOCK) technology. The nonprofit will support third-party development of COVID-19 diagnostic tests as well as gender and racial diversity in science, technology, engineering, and math using proceeds from resulting products. SHERLOCK is a method for single molecule detection of nucleic acid targets and utilizes CRISPR technology for “smart amplicon detection.” It can be adapted for use with existing diagnostic instruments, improving time to result due to the technology’s large multiplex capacity. Initial leadership of The 221b Foundation will include the president and CEO of Sherlock Biosciences as well as the assistant dean for community engagement and equity at Harvard Law School. Press release.
Researchers at North Carolina State University are developing a computational model that can be used to identify the best allocation plans for distributing COVID-19 test kits to hospitals, clinics, and relevant state agencies. The work is being supported by a one-year, $600,000 grant from the National Institute for Innovation in Manufacturing Biopharmaceuticals. The model can be updated as new information becomes available, and will be used to address key questions related to COVID-19 testing: What is the optimal distribution of reagents and test kits for allocation to selected locations? What test kits should be stockpiled for use in case of a second wave of COVID-19 infections? How should inventory and testing capacity be positioned in order to enable both the rapid distribution of test kits and the collection, transportation, and analysis of test samples? How will the system adapt to changes in patient management and testing protocols as demand for kits shifts based on patterns of new COVID cases? What are the different strategies needed for the different types of test kits (molecular, antigen and antibody)? The model will be developed for North Carolina but extend nationwide by the end of the project. The challenges include identifying all the suppliers of test kits and materials and defining what constitutes a “kit.” Press release.
The National Institutes of Health has awarded seven contracts to companies and academic institutions to develop digital health solutions that help address the COVID-19 pandemic. The work could lead to user-friendly tools like smartphone apps, wearable devices, and software that can identify and trace contacts of infected individuals, keep track of verified COVID-19 test results, and monitor the health status of infected and potentially infected individuals. The projects represent a broad range of solutions for immediate public health needs related to the pandemic, and several focus on solutions for medically underserved communities and people with limited access to healthcare who are disproportionally affected by COVID-19. Award recipients include Evidation Health, Inc. (San Mateo, California), IBM (Armonk, New York), iCrypto, Inc. (Santa Clara, California), physIQ, Inc. (Chicago, Illinois), Shee Atiká Enterprises, LLC (Sitka, Alaska), University of California, San Francisco, and Vibrent Health (Fairfax, Virginia). Separately, a contract was also awarded to CareEvolution, LLC (Ann Arbor, Michigan) for a digital health solution that integrates self-reported symptoms, data from consumer wearable devices, electronic health record and claims data, and COVID-19 test results to indicate whether users are ready to return to work and normal activities during the COVID-19 pandemic. Press release.
Siemens Healthineers has announced a collaboration with the U.S. Centers for Disease Control and Prevention and the JRC (Joint Research Centre) of the European Commission on a research project to develop a novel process for standardizing SARS-CoV-2 assays. Antibody tests differ among test manufacturers and currently cannot be analytically compared because they target different SARS-CoV-2 proteins (e.g., spike protein, S1/S2, S1 RBD, N protein). The reportable numerical patient results of the current semi-quantitative assays are also expressed in units that are not actual concentrations of antibodies, but rather the antibody activity to the virus. The new collaboration will develop a novel process for standardizing SARS-CoV-2 assays by anchoring each protein to a neutralization antibody titer. The thresholds displayed in the standardized unit of measure for IgG, arising either from natural infection or vaccination, will likely contribute to a standardized interpretation of immunity through test results. Results of the project will support the JRC's production of a reference material with assigned concentrations of antibody specific to each viral protein. Press release.
Fluidigm Corporation has announced that ImmunoGenomics (Houston) and Vero Diagnostics (Research Triangle Park) are among the Clinical Laboratory Improvement Amendments (CLIA) certified labs now offering testing services using the Advanta Dx SARS-CoV-2 RT-PCR Assay on the Fluidigm Biomark HD system. The company recently received Emergency Use Authorization from the FDA for the saliva-based assay that detects nucleic acid from the SARS‑CoV‑2 virus. In its submission to the FDA, Fluidigm showed that its assay generated results in 100% agreement with those from authorized assays based on nasopharyngeal samples. ImmunoGenomics currently processes approximately 3,000 samples per day using the Advanta Dx SARS-CoV-2 RT-PCR Assay. The Fluidigm test offers rapid turnaround time and avoids supply chain constraints of other approaches. Press release.
Care Mentor AI—a Russian provider of neural network-based computer vision services for the analysis of X-ray and computer tomography (CT) images—is using Zhores supercomputer at the Skoltech Center for Computational and Data-Intensive Science and Engineering (Russia) to estimate the severity of COVID-19 based on full 3D chest CT scans. Zhores is the first energy-efficient petaflops supercomputer in Russia and designed specifically for machine learning and data-based modeling tasks. Care Mentor AI experts report that they have trained their neural networks to detect cancers in CT images with 95% accuracy and estimate the percentage of lung damage caused by COVID-19 with 86% accuracy. The AI application also marks and prioritizes abnormalities detected in radiological images with 93% accuracy, helping doctors cope with a larger number of cases. Pilot testing of its chest X-ray screening system is underway at a Moscow clinic. The application is also being tested within the Moscow Experiment, a program that aims to test and integrate innovative computer-vision-based medical image analysis technologies in the Moscow healthcare system. Press release.