August 21, 2020 | Disturbing uptick in partner violence during the COVID-19 pandemic, ICD-10 codes insufficient for capturing COVID-19 related symptoms, the role of mobile health technologies to monitor patients at home, the role of children in community spread, and impact of different types of antibodies. Plus, neutralizing antibodies for sale.
Literature Updates
A research team led by investigators at Brigham and Women's Hospital has found an alarming increase in physical injuries associated with intimate partner violence (IPV) during the COVID-19 pandemic, based on objective signs of abuse from radiology reports and images. Their findings, published in Radiology, were based on pattern and severity of injuries related to IPV in patients at the Brigham from March 11 to May 3, 2020 relative to injuries over the previous three years. The team found 26 cases in which victims sustained physical IPV in the spring of 2020, compared to 20 in 2019, 7 in 2018 and 15 in 2017. In terms of the severity of abuse, the number of deep injuries during the pandemic was 28 compared to a total of 16 deep injuries during the previous three years. Overall, a total of 62 IPV victims of all types (physical and non-physical abuse) were identified in 2020; 104 in 2019; 106 in 2018; and 146 in 2017. Researchers theorize that victims may be so fearful of COVID-19 that they aren't seeking help until the abuse is severe. DOI: 10.1148/radiol.2020202866
Symptom-specific ICD-10 codes do not accurately capture COVID-19–related symptoms and should not be used to populate symptoms in electronic medical record (EMR)–based cohorts, according to researchers at the University of Utah. In their cohort study, published in JAMA Network Open, an EMR review of 2,201 patients tested for COVID-19 between March 10 and April 6, 2020 found that ICD-10 codes had poor sensitivity and negative predictive value for capturing fever, cough, and dyspnea. This inaccuracy has implications for any downstream data model, scientific discovery, or surveillance that relies on these codes, they say. DOI: 10.1001/jamanetworkopen.2020.17703
University of Southern California researchers have found the likely order in which COVID-19 symptoms first appear—fever followed by cough, muscle pain, and then nausea and/or vomiting and diarrhea. This may help patients seek care promptly or decide sooner rather than later to self-isolate, as well as help doctors rule out other illnesses and perhaps intervene earlier in the disease, they say. The authors predicted the order of symptoms from the rates of symptom incidence of more than 55,000 confirmed coronavirus cases in China, all of which were collected from Feb. 16-Feb. 24, 2020, by the World Health Organization. They also studied a dataset of nearly 1,100 cases collected from Dec. 11, 2019 through Jan. 29, 2020, by the China Medical Treatment Expert Group via the National Health Commission of China. Results published in Frontiers in Public Health. DOI: 10.3389/fpubh.2020.00473
An international task force has concluded that mobile health technologies are a viable option to monitor COVID-19 patients at home and predict which ones will need medical intervention, in research that published in IEEE Open Journal of Engineering in Medicine and Biology. The technologies—including wearable sensors, electronic patient-reported data and digital contact tracing—also could be used to monitor and predict coronavirus exposure in people presumed to be free of infection, providing information that could help prioritize diagnostic testing. The panel was comprised of 60 members from Australia, Germany, Ireland, Italy, Switzerland and across the U.S., which represented researchers and experts from fields that included computer science, biomedical engineering, medicine and health sciences. The paper identifies 12 examples of technologies that could potentially be used to monitor patients and healthcare workers, among them smartphone applications enabling self-reports, wearable sensors enabling physiological data collection, and wearable sensors to capture heart rate and sleep duration. DOI: 10.1109/OJEMB.2020.3015141
An article in the Journal of Medical Microbiology describes a new rapid molecular test called N1-STOP-LAMP that is 100% accurate in diagnosing samples containing SARS-CoV-2 at high loads in 20 minutes. N1-STOP-LAMP is a “near care” test and not intended to replace current gold standard PCR testing. But the test’s high accuracy and ease of use make it a prime candidate for use in settings with limited testing capabilities, the Australian development team report. The method involves using a small portable machine the size of a shoebox that can reliably detect SARS-CoV-2 from just one nasal swab. The N1-STOP-LAMP method correctly identified 87% of tests as positive when used to assess 157 confirmed-positive samples, with results produced in an average of 14 minutes for 93 of those clinical samples. DOI: 10.1099/jmm.0.001238
An online COVID-19 symptom tracking tool developed by researchers at Georgetown University Medical Center ensures a person's confidentiality while being able to actively monitor their symptoms. The tool is not proprietary and can be used by entities that are not able to develop their own tracking systems. Details of the COVID19 Symptom Tracker and a pilot study published in the Journal of Medical Information Research. The internet tool assigns a unique identifier as people enter their symptoms and other relevant demographic data and allows institutions to generate reports about items on which people can act (e.g., symptoms that might require medical attention). People using the system are provided with information and links to Centers for Disease Control and Prevention COVID-19 recommendations and instructions for how people with symptoms should seek care. The tool launched on March 20, followed by initial testing of the system with the voluntary participation of 48 Georgetown University School of Medicine students or their social contacts. A Spanish language version has also been released. DOI: 10.2196/19399
Asymptomatic patients are less likely to infect close contacts compared to severe cases, and secondary transmission acquired from public transportation is rare, conclude researchers from Southern Medical University (Guangzhou, China) and the Guangzhou Center for Disease Control and Prevention. They traced more than 3,410 close contacts of 391 COVID-19 index cases between January and March 2020 to evaluate the risk for disease transmission in different settings. Risk for secondary transmission was found to be less than 4% among close contacts of persons with COVID-19, but one in 10 household contacts was found to be infected. Manifestation of certain symptoms, such as expectoration, was also associated with an increased risk for infection among close contacts of index cases. Results published in the Annals of Internal Medicine. DOI: 10.7326/M20-2671
Two different types of detectable antibody responses in SARS-CoV-2 tell very different stories and may indicate ways to enhance public health efforts against the disease, according to researchers at The University of Texas MD Anderson Cancer Center. Antibodies to the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection, while the SARS-CoV-2 nucleocapsid protein (N-protein) antibody may often only indicate exposure to the virus, not protections against reinfection. The results, published in JCI Insight, highlight findings from a quantitative serological enzyme-linked immunosorbent assay using SARS-CoV-2 S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from confirmed COVID-19 hospitalized patients and 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Results showed that 3% of healthy and non-COVID-19 samples collected during the pandemic in Houston were positive for the N-protein antibody, but only 1.6% of those had the S-RBD antibody. Of samples with the S-RBD antibody, 86% had neutralizing capacity vs. only 74% of the samples with N-protein. When positive for both, 96.5% exhibited neutralizing capacity. Some commercially available serological tests confirm only the presence of antibodies to the N-protein. Results could aid in rapid assessment of the efficacy of vaccine candidates as they are translated into the broader population DOI: 10.1172/jci.insight.142386
Researchers at Johns Hopkins University School of Medicine studying tissue removed from patients’ nose during endoscopic surgery believe they may have discovered the reason why so many people with COVID-19 lose their sense of smell, even when they have no other symptoms—extremely high levels of angiotensin converting enzyme II (ACE-2) only in the area of the nose responsible for smelling. Their findings, published in the European Respiratory Journal, offer clues as to why COVID-19 is so infectious and suggest that targeting this part of the body could potentially offer more effective treatments. In addition to surgically removed tissue samples from the olfactory epithelium of 23 patients, the research team also studied biopsies from the trachea of seven patients; none of the patients had been diagnosed COVID-19. The levels of ACE2 in olfactory epithelium cells was between 200 and 700 times higher than other tissue in the nose and trachea, and similarly high levels were found in all the samples regardless of whether the patient had been treated for chronic rhinosinusitis or another condition. ACE2 was not detected on olfactory neurons, the nerve cells that pass information about smells to the brain. DOI: 10.1183/13993003.01948-2020
A research team from the University Hospital at Ruhr-Universität Bochum (Germany) has developed a test that provides information on the immune response to SARS-CoV-2 in patients who need to take immunosuppressive drugs, including those who had had an organ transplant. Immunosuppressive therapy can be adapted individually during a COVID-19 infection using the test. Findings were reported in the American Journal of Transplantation. The test was developed in the immunodiagnostics laboratory at Marien Hospital Herne. DOI: 10.1111/ajt.16252
In the most comprehensive study of COVID-19 pediatric patients to date, Massachusetts General Hospital and Mass General Hospital for Children (MGHfC) researchers provide critical data showing that children play a larger role in the community spread of COVID-19 than previously thought. In a study of 192 children ages 0-22, 49 tested positive for SARS-CoV-2, and another 18 had late-onset, COVID-19-related illness. The infected children had a significantly higher level of virus in their airways than hospitalized adults in ICUs for COVID-19 treatment. Lower numbers of the virus receptor in younger children did not correlate with a decreased viral load. The researchers also studied immune response in Multisystem Inflammatory Syndrome in Children that can develop several weeks after SARS-CoV-2 infection to discover that the heart seems to be the favorite organ targeted for serious systemic complications, as in adults. Findings from nose and throat swabs and blood samples from the MGHfC Pediatric COVID-19 Biorepository carry implications for the reopening of schools, daycare centers and other locations with a high density of children and close interaction with teachers and staff members, researchers note. The study published in the Journal of Pediatrics. DOI: 10.1016/j.jpeds.2020.08.037
Mild cases of COVID-19 can trigger robust memory T cell responses, even in the absence of detectable virus-specific antibody responses, researchers report in Cell. To date, there is limited evidence of reinfection in humans with previously documented COVID-19 and most studies of immune protection against SARS-CoV-2 in humans have focused on the induction of neutralizing antibodies that tend to wane and are not detectable in all patients. Here, researchers assessed SARS-CoV-2-specific T cell and antibody responses in more than 200 individuals from Sweden across the full spectrum of exposure, infection, and disease. During the acute phase of infection, the T cell responses were associated with various clinical markers of disease severity. After recovery, the strongest T cell responses were present in individuals who had a severe course of the disease. Progressively lower T cell responses were observed in individuals who recovered from very mild COVID-19, and family members exposed to the virus, but were detectable months after infection and sometimes in the absence of SARS-CoV-2-specific antibodies. Findings suggest that reliance on antibody responses may underestimate the extent of population-level immunity against SARS-CoV-2. DOI: 10.1016/j.cell.2020.08.017
A second study by the same research team at the University of Sydney (Australia), newly published in Transboundary and Emerging Diseases, confirms the association between lower humidity and an increase in community transmission of COVID-19. The study estimated that for a 1% decrease in relative humidity, patient cases might increase by 7%-8%. That’s equivalent to a twofold increase in COVID-19 notifications per a 10% drop in relative humidity, raising the prospect of seasonal disease outbreaks. Reduced humidity was found in several different regions of Sydney to be consistently linked to increased cases, and the same link was not found for other weather factors such as rainfall, temperature or wind. DOI: 10.1111/tbed.13766
Smell disorder experts in Europe have shown how smell loss associated with COVID-19 infection differs from what is typically experienced with a bad cold or flu. The main differences are that COVID-19 can breathe freely, do not tend to have a runny or blocked nose, and cannot detect bitter or sweet tastes. These findings, published in Rhinology, lend weight to the theory that COVID-19 infects the brain and central nervous system. For the small study, the research team carried out smell and taste tests on 10 COVID-19 patients, 10 people with bad colds and a control group of 10 healthy people, all matched for age and sex. DOI: 10.4193/Rhin20.251
In an article published in npj Digital Medicine, a Harvard Medical School-led multi-institutional research team describe a COVID-19 centralized medical records repository that they’ve created for the purpose of rapid data collection and data analysis and visualization. The platform contains data from 96 hospitals in five countries (U.S., France, Italy, Germany and Singapore) and has yielded intriguing, albeit preliminary, clinical clues about how the disease presents, evolves and affects different organ systems across different categories of patients with COVID-19. For now, the platform represents more of a proof-of-concept than a fully evolved tool, the research team cautions, with initial observations enabled by the data raising more questions than they answer. Their report provides insights from early analysis of records from 27,584 patients and 187,802 lab tests collected in the early days of epidemic, from Jan. 1 to April 11. Among the long list of reported observations are variation by country of patient age, remarkably consistent lab test findings, and major abnormalities evident on day one of diagnosis for C-reactive protein and D-dimer protein with test results progressively worsening in patients who went on to develop more severe disease or died. The participating countries are part of the Consortium for Clinical Characterization of COVID-19 by EHR. DOI: 10.1038/s41746-020-00308-0
University of California, Irvine (UCI) scientists have created a robust, low-cost imaging platform utilizing lab-on-a-chip technology that may be available for rapid coronavirus diagnostic and antibody testing nationwide by the end of the year. The test, described in the journal Lab on a Chip, uses blood from a finger prick to probe hundreds of antibody responses to 14 respiratory viruses, including SARS-CoV-2, in two to four hours. The results are printed on a low-cost imaging platform (TinyArray imager) that combines a 3D-printed prototype with an off-the-shelf LED and a small 5-megapixel camera to find markers for many antibodies simultaneously. This, the authors say, ensures accuracy equal to that of expensive imaging systems but makes the platform portable enough to deploy anywhere at a cost of only $200. The same device can also process the results of commonly used nose swab tests for SARS-CoV-2 so that patients can be tested for COVID-19 and its antibodies on a single platform. The UCI team has already completed 5,000 tests in Orange County, and the final goal is to test 20,000 samples per unit a day. To scale up production of the TinyArray imager, they’re partnering with UCI startups Velox Biosystems Inc. and Nanommune Inc. They expect the platform will be ready to deploy across the U.S. by the end of 2020 and are working with scientists in Uruguay, Russia and Thailand to develop similar systems for their nations. DOI: 10.1039/D0LC00547A
Meanwhile, a team of researchers in China report in ACS Nano report that they have developed the prototype for a nanomaterial-based sensor to non-invasively detect COVID-19 in the exhaled breath of infected patients—akin to a breathalyzer test for alcohol intoxication. Previous studies have shown that viruses and the cells they infect emit volatile organic compounds (VOCs) that can be exhaled in the breath. The researchers made an array of gold nanoparticles linked to molecules that are sensitive to various VOCs (when VOCs interact with the molecules on a nanoparticle, the electrical resistance changes). They trained the sensor to detect COVID-19 by using machine learning to compare the pattern of electrical resistance signals obtained from the breath of 49 confirmed COVID-19 patients with those from 58 healthy controls and 33 non-COVID lung infection patients. Once machine learning identified a potential COVID-19 signature, the team tested the accuracy of the device on a subset of participants. In the test set, the device showed 76% accuracy in distinguishing COVID-19 cases from controls and 95% accuracy in discriminating COVID-19 cases from lung infections. The sensor could also distinguish, with 88% accuracy, between sick and recovered COVID-19 patients. DOI: 10.1021/acsnano.0c05657
A Louisiana State University (LSU) Health New Orleans radiologist and evolutionary anatomist have teamed up to show the same techniques used for research on reptile and bird lungs can be used to help confirm the diagnosis of COVID-19 in patients. Their paper, published in BMJ Case Reports, demonstrates that 3D models are a strikingly clearer method for visually evaluating the distribution of COVID-19-related infection in the respiratory system. They created 3D digital models from CT scans of patients hospitalized with symptoms associated with SARS-CoV-2. Three patients who were suspected of having COVID-19 underwent contrast-enhanced thoracic CT when their symptoms worsened. Two tested positive for SARS-CoV-2, one of whom was reverse transcription chain reaction (RT-PCR) negative but this was presumed to be a false negative due to compelling clinical and imaging findings. CT features can range in form and structure and appear to correlate with disease progression, they say, helping to establish diagnosis. CT scans were all segmented into 3D digital surface models using the scientific visualization program Avizo (Thermo Fisher Scientific) and techniques used at LSU for evolutionary anatomy research. DOI: 10.1136/bcr-2020-236943
Industry Updates
Absolute Antibody has announced the availability of SARS-CoV-2 neutralizing antibodies derived from individuals infected with COVID-19. The antibodies, originally generated by Fred Hutchinson Cancer Research Center, have been engineered into recombinant formats useful for COVID-19 research and diagnostic development. Two antibody clones are available: CV1 and CV30, each bound the SARS-CoV-2 spike glycoprotein, with CV30 also shown to bind the receptor binding domain (RBD) and inhibit the interaction with the host cell receptor ACE2. Both antibodies are now available in a variety of species, isotypes and subtypes designed to extend their usefulness in COVID-19 applications. They are now available to scientists and diagnostic developers worldwide via Absolute Antibody’s online catalog. Press release.
A Penn State aerospace engineer who specializes in developing materials for use in space is developing a stretchable sensor and foldable field hospital that could aid in the COVID-19 pandemic. The first step is to develop the stretchable sensor (actually many sensors connected into one network) that would fit to patients’ chest and abdomen to monitor their breathing, temperature and coughing—three of the most important vital signs to know when it comes to this virus. By making the sensor foldable, it could compress into a small package for storage and transportation. The wearable sensor will pair with an antenna, which would remove the need for wires or batteries. Development of the field hospital will begin with an easy-to-assemble unit that can hold one to two patients and fold into a container the size of a large suitcase. The research is funded by the National Science Foundation and will involve Penn State undergraduates. Press release.