May 29, 2020 | This week has seen diagnostics continue to play a vital role in combating the COVID-19 pandemic. Telehealth platforms are continuing to expand, and new studies report that, independent/assisted living facilities, testing is a better strategy for identifying staff and older adults with COVID-19 than symptom screening. Here, we round up the week’s research and industry news for COVID-19.
Literature Updates
In independent/assisted living facilities, testing is a better strategy for identifying staff and older adults with COVID-19 than symptom screening, according to a study of 142 residents and staff exposed to persons with the virus. Adherence to social distancing and preventive guidelines may also contribute to interruption of COVID-19 transmission. The results draw a sharp contrast to reports from long-term care facilities with dramatically high transmission, morbidity and mortality from an outbreak of COVID-19 and a high percentage of asymptomatic but positive cases. The study published in JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2020.2233
Remote reading of imaging studies on home PACS workstations helps protect vulnerable staff and patients alike from COVID-19, while ensuring seamless interpretation capabilities in emergency scenarios, report University of Alabama researchers in the American Journal of Roentgenology. Implementation at their institution required a financial request from hospital administration for the hardware virtual private network system and standard display monitors. Workstations were provided emergency radiologists as well as abdominal, cardiothoracic, musculoskeletal and neuroradiology sections. DOI: 10.2214/AJR.20.23495
A study conducted by investigators at Cedars-Sinai suggests that universal COVID-19 testing of asymptomatic pregnant women in labor may be unnecessary at every hospital. Infections from the novel coronavirus and deaths from COVID-19 are strikingly lower in California than those in the state of New York, where several large hospitals reported nearly 14% of asymptomatic women admitted for childbirth had tested positive for COVID-19 during the early weeks of the pandemic. All 82 pregnant patients admitted to Cedars-Sinai for one week in April were tested and, of those, only two were symptomatic. Results published in Obstetrics & Gynecology. DOI: 10.1097/AOG.0000000000003987
A study in Australia finds the number of children and adolescents testing positive for COVID-19 at The Royal Children’s Hospital (a tertiary pediatric hospital in Melbourne) has been low and none who contracted the virus required in-hospital treatment, in the first 30 days since seeing its first patient. Out of 434 children tested for the virus, only four had a positive result and they all recovered within two weeks after experiencing mild upper respiratory symptoms. The research published in Emergency Medicine Australasia. DOI: 10.1111/1742-6723.13550
Lower levels of ACE2 nasal gene expression in children may explain why children have a lower risk of COVID-19 infection and mortality, according to a study by researchers at Mount Sinai that published in JAMA. The SARS-CoV-2 virus uses ACE2 to enter the host. ACE2 nasal gene expression in nasal epithelium increases with age and could potentially be used as a biomarker to evaluate COVID-19 susceptibility. Results were based on a retrospective examination of nasal epithelium from 305 individuals aged 4 to 60 years who had been recruited to study biomarkers of asthma. DOI: 10.1001/jama.2020.8707
A new review of findings from over 40 studies on coronavirus immunity, published in the Journal of General Virology, discusses possible implications for the COVID-19 pandemic. The article, written by top U.K. virologists, suggests that SARS-CoV-2 could become the fifth seasonal coronavirus with recurring epidemics of lessening severity over the next several years. For seasonal coronaviruses where disease is mild, there have even been reports of reinfection after as little as 80 days. The authors also discuss the currently available antibody tests for SARS-CoV-2 and explain the differences between these tests, their accuracy and limitations. DOI: 10.1099/jgv.0.001439
Among 60 patients previously diagnosed with and treated for COVID-19, 10 had RT-PCR test results positive for SARS-CoV-2 from four to 24 days after index hospital discharge, according to a study by researchers in China that published in JAMA Network Open. As discharged patients were provided with home isolation instructions and local cases were rare, their positive results were presumed to be persistent viral shedding rather than reinfection. Of the 10, six had had persistent viral shedding in the gastrointestinal tract. Lower threshold cycle values were seen with anal swabs than with nasopharyngeal swabs; however, infectivity remains unclear since infectious viruses have yet to be isolated from stool samples. DOI: 10.1001/jamanetworkopen.2020.9759
A portable analyzer capable of detecting anti-avian influenza virus antibody in blood serum within 20 minutes could be used to rapidly test for antibodies against SARS-CoV-2 if a suitable reagent is developed. The new method, developed by Hokkaido University (Japan), is based on conventional fluorescence polarization immunoassay but applies a different measurement mechanism to make the analyzer much smaller and portable. The combined use of liquid crystal molecules, an image sensor and the microfluidic device makes it possible to simultaneously examine multiple samples and reduces the volume of each sample required. As described in Sensors and Actuators B: Chemical, researchers have successfully used the analyzer with a reagent to detect anti-H5 avian influenza virus antibody. The same technology could be used to detect anti-coronavirus antibodies by reproducing fragments of spike proteins expressed by COVID-19. DOI: 10.1016/j.snb.2020.128160
Damage to the immune system in asymptomatic COVID-19 infections is milder compared with symptomatic infections, finds a study of patients in China that published in JAMA Network Open. Patients with asymptomatic SARS-CoV-2 infection also have a shorter duration of viral shedding from nasopharyngeal swabs and lower risk of a recurring positive test result of SARS-CoV-2 from nasopharyngeal swabs. Included in the study were 78 patients from 26 cluster cases of exposure to the Hunan seafood market or close contact with other patients with COVID-19, who tested positive for COVID-19 between Dec. 24, 2019 and Feb. 24, 2020. DOI:10.1001/jamanetworkopen.2020.10182
The prevalence of symptomless COVID-19 infection may be much higher than thought, reveals a study charting the enforced isolation of cruise ship passengers. More than eight out of 10 of passengers and crew who tested positive for the infection had no symptoms. The researchers, all of whom were on board the vessel carrying 128 passengers and 95 crew, describe the unfolding of events in Thorax. The potentially high rate of false-negative results obtained with current swab tests suggests secondary testing is warranted. DOI: 10.1136/thorax-jnl-2020-215091
A team of European researchers have found the loss of smell and loss of taste to be two distinct symptoms of COVID-19, based on responses to an online questionnaire by 2,153 hospitalized and ambulatory patients in 18 hospitals with mild-to-moderate disease between March 22 and April 23, 2020. Their results suggest that anosmia may not be related to nasal obstruction or inflammation. DOI: 10.7326/M20-2428
Ina study published in the Canadian Medical Association Journal, researchers at the Université de Sherbrooke in Quebec similarly report that changes in taste and loss of smell were strongly associated with SARS-CoV-2. Among 2,883 adults tested for SARS-CoV-2 for a period in March, researchers identified 134 positive cases. Almost two-thirds (63%) of these people reported either loss of smell, changes in taste or both symptoms, compared with 8% in the control group who did not have SARS-CoV-2. DOI: 10.1503/cmaj.200869
Some recovered COVID-19 patients may still be virus carriers even after they reach the basic discharge criteria, according to a single-center observational study in China published in JAMA Network Open. The phenomenon was seen in 11 of 69 patients in the study discharged from a hospital designated for patients with COVID-19 in Guizhou Province between Jan. 25 and Feb. 26, 2020. Results revealed that the interval from discharge to positive RT-PCR results was 9 to 17 days, which is longer than the interval reported by earlier research in China. The authors therefore suggest that medical institutions pay attention to the follow-up of discharged patients by closely monitoring their RT-PCR results, even if they have been in quarantine for 14 days. Findings also suggest fatigue, number of initial symptoms, and creatine kinase level could be associated with recurrent positive RT-PCR results, although further verification is required because of the limited number of patients. DOI: 10.1001/jamanetworkopen.2020.10475
Patient notes taken by general practitioners currently unavailable to medical researchers could provide important clues about “missing” COVID-19 diagnoses, based on findings of a citizens' jury study at Brighton and Sussex Medical School published in the Journal of Medical Ethics. Concerns about patient privacy is the main roadblock to use of such information, but members of the U.K. public expressed interest in making free text data available to researchers. Advances in computer science and text analytics have made it possible for them to extract specific clinical information from large quantities of patient documents and analyze many patient records at once. DOI: 10.1136/medethics-2019-105472
Researchers at Johns Hopkins have found that the chance of a false negative result from a RT-PCR test is greater than 1 in 5—and, at times, far higher. The study, which analyzed seven previously published studies on RT-PCR performance, found the probability of a false negative result decreases from 100% on day 1 of being infected to 67% on day 4 and 20% on day 8. It also found that on the day a person started experiencing actual symptoms of illness, the average false negative rate was 38%. In addition, the false negative rate began to increase again from 21% on day 9 to 66% on day 21. Results published in the Annals of Internal Medicine. DOI: /10.7326/M20-1495
A study by University of Cincinnati researchers and four Italian institutions reviewing neuroimaging and neurological symptoms in patients with COVID-19 may shed light on the virus's impact on the central nervous system. The findings, published in Radiology, reveal that altered mental status (59%) and stroke (31%) are the most common neurological symptoms in COVID-19 patients, which the authors say could help physicians notice "red flags" earlier. This is the largest and first study in the literature that characterizes the neurological symptoms and neuroimaging features in COVID-19 patients. It included images from 725 hospitalized patients in Italy with confirmed COVID-19 infection between Feb. 29 and April 4, 2020. DOI: 10.1148/radiol.2020201933
Nearly half of individuals who contract COVID-19 experience changes in their sense of taste, according to a systematic review by a multi-institutional team of researchers that has been submitted to Gastroenterology. Researchers analyzed data from five studies, collectively involving 817 patients, conducted between mid-January and the end of March. Researchers suspect the true prevalence could be even higher because some of the studies were based on reviews of patient charts, which may not have noted every symptom. Thye propose that changes to sense of taste be one of the screening symptoms—along with fever, shortness of breath and productive cough—for suspected COIVD patients as well as to identify healthy carriers of the virus in the general population. DOI: 10.1053/j.gastro.2020.05.003
In the Journal of Molecular Diagnostics, investigators at Rutgers University report that a simple salt solution commonly found in hospitals and clinical laboratories—phosphate buffered saline (PBS)—can be used as a medium to reliably transport coronavirus-contaminated specimens to the testing laboratory for periods of up to 18 hours, which is often needed in busy clinical settings. Clinical specimens suspected of containing viruses are usually shipped to testing laboratories in virus transport medium, now in severely limited supply. Researchers found that SARS-CoV-2 was detected in samples from 16 confirmed COVID-19 patients at similar levels when transported in either VTM or PBS. In a parallel experiment mimicking field conditions, in which specimens may remain in transport for longer periods, they noted storage at room temperature had little effect on the values detected for the three SARS-CoV genes in either PBS or VTM. When examining samples transported in both PBS and VTM from an additional 12 patients with unknown viral loads, they again found that the storage medium did not affect detectability of the virus. DOI: 10.1016/j.jmoldx.2020.04.209
Updates from Industry
The International Vaccine Institute (IVI, South Korea) is strengthening COVID-19 surveillance in sub-Saharan Africa, specifically Madagascar and Burkina Faso, by leveraging its network of infectious disease surveillance sites. Financial support is coming from the Swedish International Development Cooperation Agency. To supplement longer-term epidemiological and clinical studies, IVI will assist with screening and diagnosing suspected COVID-19 cases at designated healthcare centers as well as conduct a cross-sectional survey of the general population. Press release.
Children's National Hospital is expanding its telehealth platform to support 15 healthcare sites in the D.C.-Maryland-Virginia region serving children and young adults. The means is a regional pediatric telehealth consortium being created with $928,000 in funding from the Federal Communications Commission's Wireline Competition Bureau. The platform will be used to provide care to children with COVID-19 as well as those who are medically vulnerable, and to help protect healthcare workers as the pandemic threat continues. The initiative includes establishing the COVID-19 Telemedicine Command Center, staffed by a team of virtual and in-person providers and clinicians providing 24/7 coordination of telehealth activities across all consortium healthcare sites. Funding covers telehealth carts, tablets and other connected devices, the telehealth platform, telehealth equipment, augmented intelligence to treat seriously ill COVID-19 pediatric patients, and telehealth devices and data plans to provide care to underserved patients. The “virtual hospital" model will be used for emergency room, NICU and inpatient care to provide access to specialized expertise and for outpatient care of COVID-19 patients. Press release.
Faced with a limited reagent supply for COVID-19 testing, a diagnostic platform that purifies genetic material using magnetic nanoparticles is being repurposed for the job. Bio-on-Magnetic-Beads (aka BOMB) was originally developed as a do-it-yourself diagnostic methodology by researchers at the University of Otago (New Zealand) and the University of Cardiff (Wales). Its pivot to COVID-19 was expected to fill a supply shortfall in New Zealand but has instead had a bigger impact outside the country, including researchers and clinicians in the U.S., Wales, the Isle of Man, London, Norway, Estonia and Colombia. Additionally, the method is expected to improve resilience in diagnostic testing in the U.K. and be deployed at mobile testing facilities from shipping containers (OpenCell London). Press release.
A string of government-supported studies is launching in Ontario investigating a range of important COVID-19 questions, including three led by teams from Lawson Health Research Institute and Western University. These include the development of a point-of-care blood test for COVID-19 using epitopes—a peptide fragment on the virus that evokes an immune response in humans. Researchers believe the antibody test enabled by multiple epitopes is potentially more sensitive and specific than tests that rely on a single viral protein. Identification of these epitopes are also the necessary first step to devise strategies to produce virus-neutralizing antibodies to treat those who are severely ill and inform epitope-vaccine development for COVID-19. Press release.
The Innovation Hub at West Virginia University is working with WVU Medicine to churn out up to 10,000 swabs weekly to meet demands for COVID-19 tests. The swabs have been in production at WVU in recent weeks following a request from state officials and the West Virginia National Guard. Select health departments across the state have been offering free COVID-19 testing. The swabs are being produced in collaboration with Formlabs, a 3D-printing technology developer and manufacturer based in Somerville, Massachusetts. The Innovation Hub launched in the spring in response to the COVID-19 pandemic. Press release.
Students at Cranfield University (U.K.) have designed computer models that can identify COVID-19 in X-rays. The models use computer vision and artificial intelligence (AI) to analyze chest X-ray imagery and classify information that would not normally be recognized with the naked eye to assist with the diagnosis of COVID-19. The AI can detect anomalies in an X-ray, classifying which are positive for pneumonia, and then a second model is used to diagnose if the pneumonia is caused by the COVID-19 virus. While the AI model employed in the project was able to predict results with great accuracy, the research team plans to further develop new algorithms to produce even more robust and reliable results. Press release.
A researcher at Ben-Gurion University (BGU) of the Negev (Israel) has developed an electro-optical test that will identify both asymptomatic and affected carriers of the COVID-19 virus in under one minute with greater than 90% accuracy. Each test kit will cost approximately $50, far less than the standard, laboratory-based polymerase chain reaction tests. The test detects and identifies biological samples but doesn’t require a lab environment so it can be deployed at critical locations such as airports, border crossings and stadiums as well as healthcare facilities where rapid testing is required. Initial results were based on clinical trials completed on more than 150 Israelis. Ongoing trials will compare samples from COVID-19 patients with samples of patients with other diseases to detect the presence as well as the specific stage of COVID-19 infection. The plan is to submit the test for FDA accelerated approval. The method is based on the change in the resonance in the THz spectral range imposed by the coronavirus through a THz spectroscopy performed on an electronic chip designed by BGU researchers. Particles from a simple breath test or throat and nose swabs are placed on the chip with a dense array of tens of thousands of metamaterial sensors that were designed specifically for this purpose. The point-of-care device automatically records the results into a database, making it easier to track the course of the virus as well as triage and treat patients. Press release.