By Diagnostics World Staff
Sept. 4, 2020 | A CRISPR-based assay and smartphone-based molecular test, the role of children in viral spread, using pressure to concentrate samples, a patient scoring system, timetable on retesting, two tests are better than one, and deep dives on older patients. Plus, the COVID-19 Symptom Data Challenge and nine more companies get NIH grants to scale up COVID-19 testing.
A new low-cost diagnostic test for COVID-19 quickly delivers accurate results without the need for sophisticated equipment, according to a study that published in PLOS Pathogens by researchers in China. The assay, named CRISPR-COVID, leverages CRISPR-based technology and enables high-throughput detection of SARS-CoV-2 with comparable sensitivity and specificity as metagenomic next-generation sequencing within as short as 40 minutes. When produced at a large scale, the material cost of a CRISPR-COVID test could be less than 70 cents, the authors say, suggesting it is a competitive alternative both technologically and financially. DOI: 10.1371/journal.ppat.1008705
In a commissioned editorial appearing in JAMA Pediatrics, division chiefs at Children’s National Hospital offer insight on the role children might play in the spread of COVID-19. The study sparking the commentary focused on 91 pediatric patients followed at 22 hospitals throughout South Korea. The important findings, they write, are the large number of asymptomatic patients (about a fifth of the group in this study) and that children can retain symptoms for weeks and even those who are asymptomatic continue to shed the virus for a long time after initial testing. The study also raises several questions, one concerning the link between testing and transmission. A qualitative "positive" or "negative" on testing platforms may not necessarily reflect infectivity, with some positives reflecting bits of genetic material that may not be able to make someone sick or negatives reflecting low levels of virus that may still be infectious. Other key points in the article are that testing reliability may be further limited by the testers themselves, with sampling along different portions of the respiratory tract or even by different staff members leading to different laboratory results; whether asymptomatic individuals are shedding different quantities of virus than those with symptoms remains unknown; testing only for active virus ignores the vast number of individuals who may have had and cleared an asymptomatic or mild infection (an important factor for understanding herd immunity); and the study only tested for viral shedding from the respiratory tract although multiple studies have detected the virus in other bodily fluids, including stool. DOI: 10.1001/jamapediatrics.2020.3996
Scientists from the University of Cincinnati and Wright-Patterson Air Force Base report in Biomicrofluidics that a membrane-based device can concentrate the virus content of a sample of urine or saliva, which should allow for the detection of small amounts of SARS-CoV-2 in early, asymptomatic stages of COVID-19 infection. They attached a nitrogen gas tank and regulator to the device, increasing the pressure differential between sample and surroundings. The group investigated both biofluids spiked with samples of protein from the influenza A virus and HCG (human chorionic gonadotropin, indicative of pregnancy). Test results were extremely consistent, showing a concentration result of 33 times that of the original sample. Preconcentration of a 1-milliliter sample could be achieved in five minutes and even faster with higher applied pressures. DOI: 10.1063/5.0013987
Standard diagnostic methods of nasopharyngeal and oropharyngeal swabs detected more COVID-19 cases than saliva testing among patients who were asymptomatic but at high risk or who were mildly symptomatic, researchers from the University of Ottawa, Dalhousie University, and the National Microbiology Laboratory (Canada) have determined. Saliva testing nonetheless has several distinct advantages: It does not require trained staff or PPE, can be done outside testing centers, and may be better tolerated in challenging or pediatric populations. Their study published in the Annals of Internal Medicine. DOI: 10.7326/M20-4738
University of Illinois, Urbana-Champaign researchers have demonstrated a prototype of a rapid COVID-19 molecular test and a simple-to-use, portable instrument for reading the results with a smartphone in 30 minutes, which could enable point-of-care diagnosis without needing to send samples to a lab. As reported in the Proceedings of the National Academy of Sciences, the team analyzed the viral transport media, called LAMP, using a process that bypasses the RNA extraction and purification steps of RT-PCR testing. LAMP only needs one temperature (- 65 C), making it much easier to control, and works more robustly than PCR, especially when there are contaminants in the test sample. The sample can be briefly heated, the virus broken open and the genetic sequence that specifically identifies SARS-CoV-2 detected. In a head-to-head comparison, results from the LAMP assay were in agreement with PCR results, and the sensitivity and specificity of the LAMP test were documented. The researchers then incorporated the LAMP assay onto a small 3D-printed microfluidic cartridge with input slots for the sample-containing viral transport media and the LAMP chemicals. Once the two are injected, they react within the cartridge. Fast Radius Inc. (Chicago) will be manufacturing the microfluidic cartridges at scale. DOI: 10.1073/pnas.2014739117
In a letter published in The Open Public Health Journal, a professor of medicine at Ain Shams University (Cairo, Egypt) proposes a scoring system to help classify suspected COVID-19 patients based on who will require a follow-up, home isolation, quarantine or further investigations. The simple scoring system considers epidemiological evidence of exposure, clinical symptoms and signs, and investigations (if available), and can be calculated in mere minutes. DOI: 10.2174/1874944502013010413
People who've had COVID-19 should be swab tested again four or more weeks after symptoms first appeared to minimize the risk of onward infection, suggests a large population-based study in one of Italy's former coronavirus hotspots. Study findings, published in BMJ Open, show SARS-CoV-2 takes an average of 30 days to clear from the body after the first positive test result and an average of 36 days after symptoms first appear. It's not yet known how infectious a person may be in the recovery phase. Study results also indicate that the rate of false-negative test results is relatively high (1 in 5) in early convalescence. In a preliminary analysis of 4,480 people who tested positive for the virus between Feb. 26 and April 22, 1,259 achieved viral clearance (determined by at least one negative swab test after the initial positive test) and 428 died. The average time to viral clearance was 31 days from the first positive swab test. Among 1,162 patients with an initial positive test result who were re-tested an average of three times after the 30-day mark, viral clearance was detected in 60.5% and confirmed in just under 79% of those tested again after the first negative swab. DOI: 10.1136/bmjopen-2020-040380
Combining PCR and antibody tests at the point of care (POC) increases COVID-19 detection, according to researchers at the University of Cambridge (U.K.). In a recent study to be published in Cell Reports Medicine they showed that SAMBA II, a new POC PCR test for SARS-CoV-2, dramatically reduced time spent on COVID-19 “holding” wards, allowing patients to be treated or discharged far quicker than with current lab testing set-ups. The approach was used to diagnose 45 patients at Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust. A specially designed gold standard reference test has two parts—an in vitro test to see whether patients’ serum contained neutralizing antibodies and the other the standard Public Health England laboratory test looking for genetic viral material in nose/throat swabs—either of which could be positive to confirm COVID-19. Using this gold standard, 24 of the patients had COVID-19. The SAMBA II machines were developed by Cambridge spinout company Diagnostics for the Real World. A pair of finger prick antibody tests were also used to look for antibodies against the spike protein on the surface of the SARS-CoV-2 virus. Overall, the nucleic acid tests could identify eight out of ten patients with COVID-19, but when combined with the rapid antibody tests, 100% of the COVID-19 patients were correctly identified. One of the antibody tests also outperformed the other when it came to false-positive results. DOI: 10.1016/j.xcrm.2020.100099
A blood test on hospital admission showing the presence or absence of SARS-CoV-2 can identify patients at a high risk of severe COVID-19, according to researchers at Karolinska Institute and Danderyd Hospital (Sweden). Admitted patients without virus in their blood have a good chance of rapid recovery. Their study, published in Clinical Infectious Diseases, found that patients with measurable levels of SARS-CoV-2 in their blood were seven times more likely to develop critical symptoms and eight times more likely to die within 28 days. PCR was used to analyze the presence of viral RNA in blood samples taken from 167 patients. DOI: 10.1093/cid/ciaa1285
A multicentric retrospective cohort study in Paris that published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences describes the characteristics and outcomes of 821 hospitalized older patients (ages 70 and up) with confirmed COVID-19. The mean age of patients was 86 years; 58% were female, 85% had two or more comorbidities, 29% lived in an institution, and the median (interquartile range) Activities of Daily Living (ADL) core was 4. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%) and delirium (25%). The in-hospital mortality was 31%. At COVID-19 onset, the probability of in-hospital mortality was increased with male gender, ADL score, asthenia, quick Sequential Organ Failure Assessment score of 2 or higher and specific COVID-19 anomalies on chest computerized tomography. DOI: 10.1093/gerona/glaa210
Another study taking a similar look at 16,942 older adults with COVID-19 in Turkey, published in the same journal, found 51% were women, with a mean age of 71.2 years, and that their mortality rate before and after curfew was statistically different (32.2% vs. 17.9%). Through multivariate analysis of the causes of death in older patients, researchers found that male gender, diabetes mellitus, heart failure, chronic kidney disease, dementia, cancer, admission to intensive care unit, and computed tomography finding compatible with COVID-19 were all significantly associated with mortality in entire cohort. Additionally, in patients aged between 60-79 years, coronary artery disease, oxygen support need, total number of drugs, and cerebrovascular disease during hospitalization were associated with increased risk of mortality, as was acute coronary syndrome during hospitalization in patients 80 years of age and older. DOI: 10.1093/gerona/glaa219
Researchers from Hong Kong Baptist University (HKBU) report that they have developed a COVID-19 alert system that will send a message to users through a mobile app if they and an infected person have visited the same place within a time period that gives rise to risks of exposure. The system will not collect users' personal information and location data, thereby protecting individuals' privacy while alerting them on disease transmission risks associated with confirmed infection cases. HKBU plans to launch a trial run of the system on campus in the new semester with the aim of enhancing COVID-19 risks alert capability inside campus venues and during teaching and learning activities. Staff and students can join the trial voluntarily. The system can operate in venue-to-person or person-to-person tracing mode. Press release.
Catalyst @ Health 2.0 has announced the launch of The COVID-19 Symptom Data Challenge, which is seeking novel analytic approaches that use COVID-19 Symptom Survey data to enable earlier detection and improved situational awareness of the outbreak. Challenge participants will leverage aggregated data from surveys conducted by Carnegie Mellon University and the University of Maryland, in partnership with Facebook. Approaches can integrate publicly available datasets to validate and extend the predictive utility of symptom data and should assess the impact of the integration of symptom data on identifying inflection points in state, local, or regional COVID outbreaks, as well guiding individual and policy decision-making. In the first phase of the challenge, innovators submit a digital poster summarizing their approach, and judges will award five semi-finalists $5,000 each. Those semi-finalists will present their analytic approaches and three will be selected to develop a prototype and present it at a virtual unveiling event. The grand prize winner will be awarded $50,000 and the runner up will receive $25,000. Phase I applications are due Sept. 29, 2020 at 11:59:59 p.m. EST. Press release.
The National Institutes of Health (NIH) just announced $129.3 million in scale-up and manufacturing support for a new set of COVID-19 testing technologies as part of its Rapid Acceleration of Diagnostics (aka RADx) initiative. The agency is awarding contracts to nine companies for technologies that include portable point-of-care tests for immediate results and high-throughput laboratories that can return results within 24 hours. These tests add to initial awards made to seven companies on July 31. The new awardees include MatMaCorp (Lincoln, Nebraska), with a portable mini-lab that can rapidly perform multiple RT-PCR assays in a single platform; Maxim Biomedical Inc. (Rockville, Maryland), maker of a single-use, lateral-flow test strip immunoassay that can provide results in 15 minutes or less; MicroGEM International (Charlottesville, Virginia), with a portable, point-of-care device that detects SARS-CoV-2 in saliva samples using RT-PCR in 15 minutes; Aegis Sciences (Nashville, Tennessee), which has a novel coronavirus nucleic acid detection kit and distribution system for high through-put testing that uses nasal and oral swab samples; Broad Institute (Cambridge, Massachusetts), offering a high-throughput RT-PCR COVID-19 viral test using specimens from nasal swabs that will be scaled up; Ceres Nanoscience Inc. (Manassas, Virginia), with a sample prep method using Nanotrap particles that extracts and concentrates viral material to reduce processing time and improve sensitivity; Illumina (San Diego, California), whose automated sample processing and next-generation sequencing technology for COVID-19 testing will scale up; PathGroup (Nashville, Tennessee), with proven capacity to process about 10,000 COVID-19 RNA tests daily using Roche 6800 and Hologic Panther instruments; and Sonic Healthcare USA (Austin, Texas), with expanded scope and expedited timeline of a framework for large-scale COVID-19 RT-PCR testing platforms and distribution capacity. Press release.
Colorado State University has launched an initiative to provide emergency expansion of mental healthcare across the state, with a focus on suicide prevention during the pandemic. The program is being supported by a grant of almost $800,000 from the U.S. Department of Health and Human Services' Substance Abuse and Mental Health Services Administration. Colorado already had the seventh highest number of deaths by suicide in the country before the pandemic, which threatens to make that worse. The program will focus on communities and individuals at highest risk, including rural and agricultural areas, the uninsured, people with substance-use disorders, frontline healthcare workers, and those experiencing domestic violence and their children. The grant will support provider training in evidence-based practices put forth by the U.S. Centers for Disease Control and Prevention. Collaborators include the University of Colorado Health system, Crossroads Safehouse, La Familia, Sandstone Care, and the 17th Judicial District Diversion Program. Press release.