July 24, 2020 | World-first research by Monash University in Australia has been able to detect positive COVID-19 cases using blood samples in about 20 minutes and identify whether someone has contracted the virus. This, plus more, is included in this week’s COVID-19 news and research in the diagnostics industry.
Literature Updates
The Korea Brain Research Institute has discovered the elevation of ACE2 as a SARS-CoV-2 entry receptor gene expression in elderly patients with Alzheimer's disease., making them more vulnerable to COVID-19 infection. For the study, which published in the online version of the Journal of Infection, researchers assessed the risk of SARS-CoV-2 infection in patients with Alzheimer's dementia using a micro array dataset and total RNA sequencing. The team also confirmed elevated expression of the ACE2 gene in the brain tissue of the Alzheimer's disease model mice. Based on genome analysis of Alzheimer's patient groups with early-stage, mild, and severe disease, ACE2 gene expression elevates with disease progression. Study results are expected to be used as a new diagnostic method for the elderly with underlying degenerative brain diseases. DOI: 10.1016/j.jinf.2020.06.072
Racial/ethnic minority patients admitted to the hospital with COVID-19 infection are more likely to have more severe disease on chest X-rays than white/non-Hispanic patients. Study findings, from researchers at Harvard Medical School and Massachusetts General Hospital (MGH), published in Radiology. The team looked at data from 326 patients hospitalized with confirmed COVID-19 infection between March 27 and April 10, 2020, whose chest X-ray results revealed that non-white patients had significantly more severe lung disease on admission than white/non-Hispanic patients, which in turn increased the likelihood of adverse clinical outcomes, including admission to the intensive care unit, intubation and death. As expected, the disparity correlated with a combination of factors, including delay in seeking care at the hospital, higher prevalence of pre-existing comorbidities and limited English proficiency. DOI: 10.1148/radiol.2020202602
COVID-19 is associated with life-threatening blood clots in the arteries of the legs, according to another study published in Radiology. Researchers at Montefiore Medical Center say COVID-19 patients with symptoms of inadequate blood supply to the lower extremities tend to have larger clots and a significantly higher rate of amputation (25%) and death (38%) than uninfected people with the same condition. In March and April 2020, they identified 16 COVID-19-positive patients, average age 70, who underwent CT angiography of the lower extremities for symptoms of leg ischemia and they were compared with 32 COVID-19-negative patients, average age 71, who underwent CT angiography with similar symptoms in previous years and who were well matched with COVID-19 cohort for demographic and clinical characteristics. The rate of both amputation and death was only 3% among controls. DOI: 10.1148/radiol.2020202348
A rapid laboratory test—the eosinophil count—readily obtained from a routine complete blood cell count (CBC) can aid in the early recognition of COVID-19 in patients as well as provide prognostic information, according to a study published in The Journal of the American Osteopathic Association. Researchers at Coney Island Hospital, part of the New York City Health and Hospitals system, found that the absence of eosinophils on presentation can aid in early diagnosis, and in general, a persistent low count correlated with a poor prognosis for the patient. They compared the eosinophil results of routine CBC from the first 50 admitted COVID-19-positive patients with the eosinophil results of 50 patients with confirmed influenza infection at the time of presentation to the emergency department. Of the patients with COVID-19, 60% had zero eosinophils at presentation, compared to 16% of influenza patients. The proportion of zero eosinophils rose to 88% within 48 hours of admission, and continued low counts trended with mortality rates. Eosinophil counts could dramatically lower the number of people misinformed of their true diagnosis and subsequent spread of disease. DOI: 10.7556/jaoa.2020.091
In the Annals of Internal Medicine, researchers from Stanford University School of Medicine say asymptomatic donors infected with COVID-19 may pose a risk to the safety of the blood supply. They report on the case of a volunteer blood donor who was healthy on the day of donation but had detectable SARS-CoV-2 RNA levels at least 40 days after resolution of COVID-19-like symptoms. Although this case is insufficient to recommend universal SARS-CoV-2 blood screening, the authors say their institution will continue to do so. DOI: 10.7326/L20-0725
Researchers in France have found that the production and activity of interferon (IFN) type I, a marker of the response to infections, are strongly reduced in the most severe forms of COVID-19. In addition, there is a persistent blood viral load, indicating poor control of viral replication by the patient's immune system that leads to an ineffective and pathological inflammatory response. The inflammation, caused by the transcription factor NF-kB, also leads to increased production and signaling of tumor necrosis factor-alpha and the pro-inflammatory cytokine interleukin IL-6. Distinct type-I IFN responses may be characteristic of each stage of the disease, they say in their Science report. DOI: 10.1126/science.abc6027
World-first research by Monash University (Australia), published in ACS Sensors, has been able to detect positive COVID-19 cases using blood samples in about 20 minutes and identify whether someone has contracted the virus. Their methodology uses a simple agglutination assay to detect the presence of antibodies raised in response to SARS-CoV-2 infection. The discovery could see medical practitioners across the world testing up to 200 blood samples an hour. At some hospitals with high-grade diagnostic machines, more than 700 blood samples could be tested hourly, or about 16,800 each day. A patent for the innovation has been filed. DOI: 10.1021/acssensors.0c01050
A new blood test that reliably predicts outcomes for heart failure patients could inform diagnostics and treatments for COVID-19 patients as well, according to research from cardiologists at the University of Alberta that published in Circulation: Heart Failure. When examining the circulating angiotensin peptide levels in the blood of 110 people who were experiencing heart failure due to a heart attack or stroke, they found that a high ratio between beneficial peptides (angiotensin 1-7) and harmful peptides (angiotensin II) led to better outcomes no matter how severe their symptoms were. Measuring levels of either type of peptide on its own did not provide enough information. A separate article, published in European Heart Journal, explains that the link between heart failure and COVID-19 is the key role played in each disease by the enzyme ACE2—which protects the heart by increasing production of the "good guy" peptide and suppressing the renin-angiotensin system that produces the "bad guy" peptide. ACE2 has also been identified as the receptor for SARS-CoV-2. Researchers propose that the test to determine the ratio between good and bad peptides in the cardiovascular system, which involves taking a single blood draw and analyzing it with a liquid chromatography-mass spectrometry technique, be used routinely to determine the risk of adverse outcomes in both heart failure and COVID-19 patients. DOI: 10.1161/CIRCHEARTFAILURE.120.006939 and DOI: 10.1093/eurheartj/ehaa414
In an extensive review of the latest findings on COVID-19's effect on organ systems outside the lungs published in Nature Medicine, researcher-clinicians at Beth Israel Deaconess Medical Center and Columbia University Irving Medical Center note that the virus may increase patients' risk of heart attack, kidney failure and clotting disorders. Neurological symptoms may occur in about a third of patients. Patients with severe cases of COVID-19 are also at risk for strokes caused by blood clots and delirium. Their review summarizes proposed mechanisms behind these wide-ranging systemic effects and provide clinical guidance for physicians. DOI: 10.1038/s41591-020-0968-3
A study led by Albert Einstein College of Medicine and Montefiore Health System that published in the Journal of Hospital Medicine confirms the findings of the large-scale U.K. RECOVERY trial that the steroid dexamethasone reduces deaths by about one-third in COVID-19 patients on ventilators and by about one-fifth among people who need oxygen but are not on ventilators. It additionally found the same life-saving benefits with other steroid formulations—and that a common blood test (to measure levels of C-reactive protein) may identify the best candidates for steroid treatment. DOI: 10.12788/jhm.3497
At most COVID-19 testing sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases, conclude a multi-state team of U.S. researchers in a study published in JAMA Internal Medicine. However, most people at those sites likely had no detectable SARS-CoV-2 antibodies. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population. The cross-sectional study looked at 16,025 residual clinical specimens collected during March through early May in 10 cities. Six to 24 times more infections were estimated per site with seroprevalence than with COVID-19 case report data. DOI: 10.1001/jamainternmed.2020.4130
Results of the first statewide random sample study in the U.S. to measure the spread of COVID-19 indicates a general population prevalence of about 2.8% in Indiana. Findings of the study, conducted by researchers at Indiana University, published in Morbidity and Mortality Weekly Report, the U.S. Centers for Disease Control and Prevention's scientific publication. Between April 25 and May 1, researchers tested more than 4,600 Hoosiers for viral infections and antibodies of SARS-CoV-2, including more than 3,600 people who were randomly selected from a master list of Indiana residents derived from tax returns, including filers and dependents, and an additional 900 volunteers recruited through nonrandom outreach to the African American and Hispanic communities to get a more in-depth view of the virus's activity within hard-hit populations. Researchers determined that 1.7% of participants tested positive for the novel coronavirus and an additional 1.1% tested positive for antibodies. An estimated 187,802 Hoosiers were infected with COVID-19 at the time of the study, approximately 10 times higher than the confirmed cases in the state. Participants who reported living with someone who tested positive for COVID-19 had a prevalence rate of 33.6%, and 44.2% of participants who tested positive reported no symptoms during the two weeks before testing. DOI: 10.15585/mmwr.mm6929e1
Researchers at the University of Seville's School of Computer Engineering are working on a system that uses X-ray images of patients' lungs and deep learning to help diagnose COVID-19. The neural network model can distinguish between healthy patients, pneumonia patients and COVID-19 patients—an achievement made possible using a freely accessible online database that medical professionals from around the world have been feeding with lung X-rays since the onset of the pandemic. Effectiveness of the model, based on a VGG-16 neural network for the identification of pneumonia and COVID-19 using X-rays of the torso, was roughly 100%. Results published in Applied Sciences. DOI: 10.3390/app10134640
At Virginia Tech, an ultrasensitive biosensing method has been engineered that could dramatically shorten the amount of time required to verify the presence of the COVID-19 virus in a sample. The method, described in ACS Nano, detects the contents of a sampling droplet without the need for extraction or other tedious procedures. The contents of a microdroplet are condensed and characterized in minutes, drastically reducing the error margin and giving a clear picture of the materials present. The process involves placing a collected sample into a liquid, which is then introduced into an engineered substrate surface with both high and low friction regions. A nanoantenna coating creates stop-and-go waterslides allowing water droplets to be directed and transported in a programmable and reconfigurable fashion. Prescribed spots with the nanoantennae are established as active sensors, and laser-enabled feedback allows for fast sensing and analysis. In a matter of minutes, the fingerprint spectrum and frequency of the coronavirus can be quickly picked out of a lineup of the returned data. DOI: 10.1021/acsnano.0c04239
Unsupervised home mid-nasal swab collection was found to be comparable to clinician-collected nasopharyngeal swab collection for detection of SARS-CoV-2 in symptomatic patients, particularly those with higher viral loads, say researchers from the University of Washington and Seattle Children’s Research Institute in a letter published in JAMA Network Open. Unsupervised home self-swab collection is safe and scalable in the pandemic setting, permitting widespread testing of symptomatic participants early in illness and the potential for prompt self-isolation and contract tracing. The sensitivity of home self-collection in their 185-participant study was lower than previously described, and false-negative results in samples with low initial viral loads was observed. DOI: 10.1001/jamanetworkopen.2020.16382
To better understand the symptomatology of COVID-19 in its mild forms, and potentially develop a clinical evaluation tool, researchers in France and Switzerland examined clinical data from more than 1,500 patients who underwent a PCR test between March 24 and May 7, 16% of whom tested positive for COVID-19. The clinical picture established for these patients was significantly different from that described in the hospital setting, but consistent with informal information collected previously. Among the ambulatory population, loss of taste and smell were among the most predictive symptoms of the disease. The clinical prediction score typically used, which is based on hospital data, was found useful in this study only for a subgroup of women in their 40s to 60s whose symptoms seemed more pronounced and therefore easier to detect. Results appeared in the Journal of General Internal Medicine. DOI: 10.1007/s11606-020-05933-9
In a paper in the New England Journal of Medicine, scientific leaders from the National Institutes of Health set forth a framework to increase significantly the number, quality and type of daily tests for detecting SARS-CoV-2 and help reduce inequities for underserved populations that have been disproportionally affected by the disease. They discuss establishment of the Rapid Acceleration of Diagnostics (RADx) program and the need for reliable, rapid, point-of-care testing diagnostics. RADx includes four major components to enable approximately 6 million daily tests in the U.S. by December 2020, many times the current daily testing rate. DOI: 10.1056/NEJMsr2022263
A study by researchers at the University of California – Los Angeles Health Sciences shows that in people with mild cases of COVID-19 the antibodies against SARS-CoV-2 drop sharply over the first three months after infection, decreasing by roughly half every 36 days on average. If sustained at that rate, the antibodies would disappear within about a year. An incorrect rate of 73 days was previously reported due to a math miscalculation in the study, published in the New England Journal of Medicine. The researchers studied 20 women and 14 men and antibody tests were conducted at an average of 36 days and 82 days after the initial symptoms of infection. The findings raise concerns about antibody-based "immunity passports," and may have implications for the durability of antibody-based vaccines.
Industry Updates
PerkinElmer has announced the launch of a dry blood spot (DBS) based test for SARS-CoV-2 IgG using its GSP/DELFIA platform, enabling processing of up to 5,000 samples per day. The finger-prick sample collection device allows for both decentralized sample collection and high-throughput testing. The product is being marketed as a CE-IVD test, and the Company plans to apply for Emergency Use Authorization (EUA) with the U.S. Food and Drug Administration (FDA). The DBS assay is run on PerkinElmer’s GSP analyzer, a fully automated and high throughput system for large population testing. The GSP combined with the universal TRF (time resolved fluorescence) of the DELFIA platform screens more than 30% of all newborn babies worldwide, spanning 32 countries. The traceable DBS workflow consists of five main elements: sample collection, punching, measurement on the GSP analyzer, reagents, and software, to detect anti-SARS-CoV-2 IgG antibodies. The SARS-CoV-2 IgG assay can also be run with serum or plasma samples via the Company’s Victor2™D platform. With an install base of over 2,500 GSP and Victor2D instruments, the capability for laboratories to meet heightened demand for COVID-19 testing is robust. Press release.
Israel’s Sheba Medical Center, Tel HaShomer, the largest hospital in the Middle East, announces the launch of a pilot program for breakthrough rapid COVID-19 detection tests conceived by Newsight Imaging, an Israeli startup. Sheba’s pilot program will conduct tests using Newsight’s revolutionary spectral device based on its developed Spectrometer-on-Chip. The device, which is about the size of a computer mouse, can identify and classify evidence of a virus in the body in less than one second, using a sample of fluid (blood serum or saliva sample) inserted into a disposable test cuvette. This spectral technology for virus detection itself is not the actual innovation, however. The new technological advance is Newsight’s ability to bring an expensive device that typically costs hundreds of thousands of dollars to be implemented in a single cost-effective chip, using an AI algorithm to separate the profile of a human infected with a specific virus, from a human infected with a different virus or from a healthy human. Press release.
Gnome Diagnostics is utilizing Fluidigm microfluidics technology and reagents in a test developed to detect the SARS‑CoV‑2 virus, which causes COVID-19. The Rapid Turnaround Real-Time RT-PCR COVID-19 Test, which can be performed via oropharyngeal, nasopharyngeal and nasal swab, is intended to meet growing testing needs for patients, health care workers and other critical populations across central Ohio. GnomeDX has filed for Emergency Use Authorization (EUA) for its extraction-free GnomeDX RT-PCR COVID-19 Test from the U.S. Food and Drug Administration (FDA). Press release.
A researcher at George Mason University is working to determine whether COVID-19 could be diagnosed via sweat metabolites. The concentrations of the biochemical content in human sweat have been measured using reagent kits and instruments, such as spectrophotometers. With this research, relevant spatial information will be integrated with a corresponding spectral signature to enable the diagnosis through advanced image processing and pattern recognition techniques. The proposed COVID-19 detector will be assessed using standard performance metrics of machine learning algorithms and compared to tampon-based testing methods. Press release.
A partnership among global business transformation company Altimetrik, the Vattikuti Foundation, Henry Ford Health System and the City of Detroit has provided more than 20,000 on-site COVID-19 tests to residents in 163 of Detroit's senior and congregate living facilities, as well as the city's first responders and essential workers. The partnership has been a critical part of addressing the COVID-19 pandemic in the hard-hit Detroit area. As of July 19, the State of Michigan has had approximately 7,524 confirmed cases of COVID-19 among residents of long-term care (LTC) facilities, of whom 1,973 have died due to the virus. The deaths among LTC facility residents represents roughly 31% of Michigan's total number of 6,373 deaths due to COVID-19. Press release.
In a U.K.-first, Queen Mary University of London is leading a clinical trial of a rapid PCR-based testing system for COVID-19 that delivers results in under an hour. Working with the East London Health and Care Partnership, up to 2,000 staff and residents in 50 care homes are being recruited to see how effective daily COVID-19 testing with a simple nose swab is at reducing rates of infection, hospitalization and deaths. The new testing system was developed in the U.K. by Novacyt and uses the COVID-19 PCR test already in use in NHS laboratories. The trial involves residents, staff and visitors in 25 care homes receiving daily testing on machines with the ability to process up to 100 samples a day. As a comparison, the other 25 care homes will receive the standard central laboratory testing once a week. Press release.
Georgia State University researchers are working on a SARS-CoV-2 detection with a fast turnaround time and greatly decreased false-negative outcomes. The simplified testing method uses electrochemistry to bypass the need for sample treatment or amplification by using a sensor to detect genetic sequences specific to the virus. If the RNA sequence is present, it interacts with the sensor and switches on the circuit so electrons flow to create current signal. This allows scientists and clinicians to detect tiny amounts of the virus in a sample and provides the quantity of a patient sample's viral load by measuring the intensity of these interactions or how quickly they occur. Press release.