Updated: Jun 5, 2020
App determines COVID-19 disease severity using artificial intelligence, biomarkers
Date: June 3, 2020
Source: New York University
Summary:A new mobile app can help clinicians determine which patients with the novel coronavirus (COVID-19) are likely to have severe cases. Created by researchers at NYU College of Dentistry, the app uses artificial intelligence (AI) to assess risk factors and key biomarkers from blood tests, producing a COVID-19 'severity score.'Share:
FULL STORY A new mobile app can help clinicians determine which patients with the novel coronavirus (COVID-19) are likely to have severe cases. Created by researchers at NYU College of Dentistry, the app uses artificial intelligence (AI) to assess risk factors and key biomarkers from blood tests, producing a COVID-19 "severity score."
Current diagnostic tests for COVID-19 detect viral RNA to determine whether someone does or does not have the virus -- but they do not provide clues as to how sick a COVID-positive patient may become.
"Identifying and monitoring those at risk for severe cases could help hospitals prioritize care and allocate resources like ICU beds and ventilators. Likewise, knowing who is at low risk for complications could help reduce hospital admissions while these patients are safely managed at home," said John T. McDevitt, PhD, professor of biomaterials at NYU College of Dentistry, who led the research.
"We want doctors to have both the information they need and the infrastructure required to save lives. COVID-19 has challenged both of these key areas." Creating a Severity Score
Using data from 160 hospitalized COVID-19 patients in Wuhan, China, the researchers identified four biomarkers measured in blood tests that were significantly elevated in patients who died versus those who recovered: C-reactive protein (CRP), myoglobin (MYO), procalcitonin (PCT), and cardiac troponin I (cTnI). These biomarkers can signal complications that are relevant to COVID-19, including acute inflammation, lower respiratory tract infection, and poor cardiovascular health.
The researchers then built a model using the biomarkers as well as age and sex, two established risk factors. They trained the model using a machine learning algorithm, a type of AI, to define the patterns of COVID-19 disease and predict its severity. When a patient's biomarkers and risk factors are entered into the model, it produces a numerical COVID-19 severity score ranging from 0 (mild or moderate) to 100 (critical).
The model was validated using data from 12 hospitalized COVID-19 patients from Shenzhen, China, which confirmed that the model's severity scores were significantly higher for the patients that died versus those who were discharged. These findings are published in Lab on a Chip, a journal of the Royal Society of Chemistry.
As New York City emerged as the epicenter of the pandemic, the researchers further validated the model using data from more than 1,000 New York City COVID-19 patients. To make the tool available and convenient for clinicians, they developed a mobile app that can be used at point-of-care to quickly calculate a patient's severity score.
A Clinical Decision Support Tool
The app has been retrospectively evaluated in the Family Health Centers at NYU Langone in Brooklyn, which serve more than 102,000 patients each year as one of the nation's largest Federally Qualified Health Center networks.
"Real time clinical decision support tools for COVID-19 can be extremely helpful, particularly in the outpatient setting, to help guide monitoring and treatment plans for those at greatest risk," said Isaac P. Dapkins, MD, chief medical officer for the Family Health Centers at NYU Langone and a co-author on the Lab on a Chip study. After optimizing the clinical utility of the app at the Family Health Centers at NYU Langone in May, the researchers aim to roll it out nationwide in the coming weeks. It is possible that the COVID-19 severity score could be integrated with electronic health records, thereby providing clinicians with actionable information at an early stage for those diagnosed with COVID-19.
"We hope this tool can help identify those at high risk for adverse outcomes and reduce the health disparities present with COVID-19," said Larry K. McReynolds, executive director for the Family Health Centers at NYU Langone.
Building on Innovations in Testing
The COVID-19 severity score leverages a model McDevitt previously developed to predict outcomes for patients with cardiac disease. Cardiac health is one of several priorities of McDevitt's lab, which creates point-of-care diagnostic systems that can be programmed to test for oral cancer, cardiac disease, and now COVID-19 biomarkers. The diagnostic system uses small, non-invasive samples -- such as swabs of saliva or drops of blood from a fingertip -- which are added to credit card-sized cartridges armed with bio-nano-chips pioneered by McDevitt. The cartridge is inserted into a portable analyzer that simultaneously tests for a range of biomarkers, with results available in less than half an hour.
Because this technology is currently used for research and informational purposes only, the COVID-19 app can be used with existing laboratory tests and requires oversight by an authorized clinician. However, over the next few months, McDevitt's laboratory, in partnership with SensoDx, a company spun out of his lab, plans to develop and scale the ability to test a drop of blood for COVID-19 severity biomarkers -- similar to how a person with diabetes tests their blood sugar -- and produce a severity score on the spot. "With COVID-19, point-of-care testing, coupled with a decision support system, could improve how clinicians triage patients -- and potentially improve their outcomes, particularly for those who need more immediate and aggressive care," said McDevitt. In addition to McDevitt's research group at NYU College of Dentistry, the study involved collaborators from NYU Grossman School of Medicine, NYU Tandon School of Engineering, Zhongnan Hospital of Wuhan University, and Latham BioPharm Group. The app was developed by McDevitt's laboratory and OraLiva, a company founded by McDevitt, and is available for both Apple and Android devices. The app is designated for use by authorized clinicians and is not intended for general use by patients.
Funding for the research was provided by the National Institute of Dental and Craniofacial Research (3U01DE017793-02S1 and 5U01DE017793-2). Story Source: Materials provided by New York University. Note: Content may be edited for style and length. Journal Reference:
Michael P. McRae, Glennon W. Simmons, Nicolaos J. Christodoulides, Zhibing Lu, Stella K. Kang, David Fenyo, Timothy Alcorn, Isaac P. Dapkins, Iman Sharif, Deniz Vurmaz, Sayli S. Modak, Kritika Srinivasan, Shruti Warhadpande, Ravi Shrivastav, John T. McDevitt. Clinical decision support tool and rapid point-of-care platform for determining disease severity in patients with COVID-19. Lab on a Chip, 2020; DOI: 10.1039/d0lc00373e
Take a look at Number 4. What is interesting to me are the comments that suggest that morbidity may be more due to the inflammatory response of the patients immune system that the virus itself.
4) HLH research points to treatment for COVID-19 cytokine storms
1) Taking inventory of which drugs the world is using to treat COVID-19
Researchers create database to categorize off-label use and look for promising leads
Date:May 27, 2020
Source:University of Pennsylvania School of Medicine
Summary:New research catalogued every COVID treatment documented in medical literature so far and found physicians have reported on the use of more than 100 different off-label and experimental treatments.Share:
FULL STORY With doctors and researchers around the world searching for effective treatments for COVID-19, many drugs approved to treat other diseases are being used in hopes that they'll be effective against the virus, a use that's known as "off-label." New research from the Perelman School of Medicine at the University of Pennsylvania catalogued every use documented in medical literature so far and found physicians have reported on the use of more than 100 different off-label and experimental treatments. The effort, called COvid19 Registry of Off-label & New Agents (CORONA), is an attempt to take an inventory of what's being used where, as well as to spot any evidence of treatments that warrant further investigation in a randomized clinical trial.
The findings published in Infectious Diseases and Therapy today.
"We can't win this fight if we don't take stock of the tools that are already being used and search for new ones that could be effective. While off-label use is happening all over the world, there's currently no system in place to track it, so we felt like we had to create one," said the study's lead author David C. Fajgenbaum, MD, MBA, MSc, an assistant professor of Translational Medicine & Human Genetics and director of the Center for Cytokine Storm Treatment & Laboratory (CSTL) at Penn.
Fajgenbaum is also the executive director of the Castleman Disease Collaborative Network (CDCN) and a Castleman patient himself. In 2012, after failing to respond to other therapies and having relapsed multiple times after chemo, Fajgenbaum's research suggested a drug approved for other uses may be effective for his condition. Based on his own research and in consultation with his treating physician, Fajgenbaum decided to test the drug on himself and has been in remission ever since. advertisement "With the world facing its greatest public health crisis in a century, we decided to take action, using the same approach that helped me and applying it to potentially help find promising leads in the treatment of COVID-19," Fajgenbaum said.
The team reviewed about 2,700 published papers from all over the world detailing the treatment of COVID-19. From there, they gathered data on 9,152 patients and found doctors had tried 115 different drugs. These treatments were grouped into categories -- antivirals were unsurprisingly the most common, followed by antibacterials and corticosteroids. The analysis also showed the use of immunosuppressants and blood substitutes, among other treatment options. Sheila Pierson, MS, the associate director for clinical research at the CSTL, director of registry enrollment for the CDCN, and the study's senior author, led the analysis of the data.
"Our team has spent the last several years studying drugs used to control the cytokine storm in Castleman disease, so I'm glad we were able to apply these principles to COVID19. The work remains ongoing, and we are updating this drug inventory daily as we continue to compile information on other treatments as they're being reported in the medical literature," Pierson said.
Fajgenbaum notes that the goal of this work is not to point toward the most effective treatment, but to provide a resource for what may be candidates for further study. "We hear a lot about the same handful of drugs, but we show here that there are many more currently in use than those that have already made headlines. Anything that shows promise anecdotally still needs to be rigorously tested in a clinical trial to see if it is effective and safe," Fajgenbaum said.
Additional Penn-affiliated authors and contributors on the study include Johnson Khor, Alek Gorzewski, Mark-Avery Tamakloe, Victoria Powers, Joseph J. Kakkis, Mileva Repasky, Alexander Beschloss, Laura Hernandez-Miyares, Beatrice Go, Vivek Nimgaonkar, Casey Kim, Erin Napier, Ruth-Anne Langan Pai, Sarah Frankl, Philip Angelides, Joanna Jiang, Rozena Rasheed, Duncan Mackay, Anna Wing, Michael Mayer, James Germi, Ashwin Amurthur, and Eric Rodriguez-Lopez. Story Source: Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length. Journal Reference:
David C. Fajgenbaum, Johnson S. Khor, Alexander Gorzewski, Mark-Avery Tamakloe, Victoria Powers, Joseph J. Kakkis, Mileva Repasky, Anne Taylor, Alexander Beschloss, Laura Hernandez-Miyares, Beatrice Go, Vivek Nimgaonkar, Madison S. McCarthy, Casey J. Kim, Ruth-Anne Langan Pai, Sarah Frankl, Philip Angelides, Joanna Jiang, Rozena Rasheed, Erin Napier, Duncan Mackay, Sheila K. Pierson. Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review. Infectious Diseases and Therapy, 2020; DOI: 10.1007/s40121-020-00303-8
2) Mouse model mimics SARS-CoV-2 infection in humans
Date: May 27, 2020
Source: Cell Press
Summary:A mouse model of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reproduces features observed in human patients, researchers report.
3) Clues to COVID-19 in the brain uncovered in new study
Researchers review neuro-imaging for patients and show altered mental state and stroke dominate
Date: May 27, 2020
Source: University of Cincinnati
Summary:A study reviewing neuroimaging and neurological symptoms in patients with COVID-19 may shed light on the virus's impact on the central nervous system.Share:
FULL STORY 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 the journal Radiology, reveal that altered mental status and stroke are the most common neurological symptoms in COVID-19 patients, which authors say could help physicians notice "red flags" earlier.
"Studies have described the spectrum of chest imaging features of COVID-19, but only a few case reports have described COVID-19 associated neuroimaging findings," says lead author Abdelkader Mahammedi, MD, assistant professor of radiology at UC and a UC Health neuroradiologist. "To date, this is the largest and first study in literature that characterizes the neurological symptoms and neuroimaging features in COVID-19 patients. These newly discovered patterns could help doctors better and sooner recognize associations with COVID-19 and possibly provide earlier interventions." Researchers in this study investigated neurological symptoms and imaging findings in patients from three major institutions in Italy: University of Brescia, Brescia; University of Eastern Piedmont, Novara; and University of Sassari, Sassari. Italy was the second epicenter of the spread of COVID-19, resulting in over 30,000 deaths. The study included images from 725 hospitalized patients with confirmed COVID-19 infection between Feb. 29 and April 4. Of these, 108 (15%) had serious neurological symptoms and underwent brain or spine imaging. Most patients (99%) had brain CT scans, while 16% had head and neck CT imaging and 18% had brain MRI.
Investigators found that 59% of patients reported an altered mental state and 31% experienced stroke, which were the most common neurological symptoms. Patients also experienced headache (12%), seizure (9%) and dizziness (4%), among other symptoms. "Of these 108 patients, 31, or 29%, had no known past medical history. Of these, aged 16 to 62 years, 10 experienced stroke and two had brain bleeds," Mahammedi says. "Seventy-one, or 66%, of these patients had no findings on a brain CT, out of which 7 of them (35%) brain MRI showed abnormalities."
He adds that altered mental status was more common in older adults. While results show that the neuroimaging features of patients with COVID-19 vary, and an altered mental status and stroke are the most prevalent in patients, Mahammedi says this study reveals that there are other conditions to be on the lookout for. "This topic definitely needs more research," he says. "Currently, we have a poor understanding of the neurological symptoms in COVID-19 patients, whether these are arising from critical illness or from direct central nervous system invasion of SARS-CoV-2. We hope further study on this subject will help in uncovering clues and providing better interventions for patients." Story Source: Materials provided by University of Cincinnati. Original written by Katie Pence. Note: Content may be edited for style and length. Journal Reference:
Abdelkader Mahammedi, Luca Saba, Achala Vagal, Michela Leali, Andrea Rossi, Mary Gaskill, Soma Sengupta, Bin Zhang, Alessandro Carriero, Suha Bachir, Paola Crivelli, Alessio Paschè, Enrico Premi, Alessandro Padovani, Roberto Gasparotti. Imaging in Neurological Disease of Hospitalized COVID-19 Patients: An Italian Multicenter Retrospective Observational Study. Radiology, 2020; 201933 DOI: 10.1148/radiol.2020201933
3) Tackling airborne transmission of COVID-19 indoors
Date:May 28, 2020Source:University of SurreySummary:Preventing airborne transmission of Covid-19 should be the next front of the battle against the virus, argue experts in a new article.Share:
FULL STORY Preventing airborne transmission of Covid-19 should be the next front of the battle against the virus, argue experts from the University of Surrey.
In a study published by the City and Environment Interaction journal, scientists from Surrey's Global Centre for Clean Air Research (GCARE), together with partners from Australia's Queensland University and Technology, argue that the lack of adequate ventilation in many indoor environments -- from the workplace to the home -- increases the risk of airborne transmission of Covid-19.
Covid-19, like many viruses, is less than 100mn in size but expiratory droplets (from people who have coughed or sneezed) contain water, salts and other organic material, along with the virus itself. Experts from GCARE and Australia note that as the water content from the droplets evaporate, the microscopic matter becomes small and light enough to stay suspended in the air and over time the concentration of the virus will build up, increasing the risk of infection -- particularly if the air is stagnant like in many indoor environments.
The study highlights improving building ventilation as a possible route to tackling indoor transmission of Covid-19. Professor Prashant Kumar, lead author and the Director of the GCARE at the University of Surrey, said: "These past months, living through the Covid-19 crisis, has been truly unprecedented, but we must turn this global tragedy into an opportunity to better prepare for similar threats. An improved indoor ventilation is an important step that can be taken to reduce the risk of infection. However, more must be done to recognise and understand airborne transmission of Covid-19 and similar viruses, to minimise the build-up of virus-laden air in places typically containing high densities of people." Story Source: Materials provided by University of Surrey. Note: Content may be edited for style and length. Journal Reference:
Prashant Kumar, Lidia Morawska. Could fighting airborne transmission be the next line of defence against COVID-19 spread? City and Environment Interactions, 2019; 4: 100033 DOI: 10.1016/j.cacint.2020.100033
4) HLH research points to treatment for COVID-19 cytokine storms
How mice that model immune disease's cytokine storms may point to solution for global pandemic
Date: May 28, 2020
Source:Cincinnati Children's Hospital Medical Center
Summary:A transgenic mouse developed to model the deadly childhood immune disease HLH (hemophagocytic lymphohistiocytosis) may play a key role in saving lives during the COVID-19 virus pandemic
FULL STORY A transgenic mouse developed at Cincinnati Children's to model the deadly childhood immune disease HLH (hemophagocytic lymphohistiocytosis) may play a key role in saving lives during the COVID-19 virus pandemic. One of the genetically engineered mouse strain's inventors -- Cincinnati Children's cancer pathologist Gang Huang, PhD -- is co-investigator on a small clinical trial that successfully tested a drug used to treat to HLH (ruxolitinib) to dramatically reverse respiratory and multi-system inflammation in severely ill COVID-19 patients. Data from the Phase II clinical study is published in the Journal of Allergy and Clinical Immunology. The study involved 43 hospitalized patients diagnosed with severe COVID-19 between February 9 and February 28 in Wuhan, China, believed to be ground zero for the pandemic. The multi-center study was led by Jianfeng Zhou, MD, PhD, Department of Hematology at Tongji Hospital, Tongji Medical College and Huazhong University of Science in Wuhan. Zhou is a longtime collaborator of Huang and colleagues at the Cincinnati Children's HLH Center of Excellence, part of the Cancer and Blood Diseases Institute.
Ruxolitinib Shows Signs of Benefit
Patients taking ruxolitinib were randomly selected to receive two daily 5mg oral doses of the anti-inflammatory drug, plus the standard of care treatment for COVID-19. A randomly selected control group of 21 patients received a placebo along with the standard of care treatment.
"Ruxolitinib recipients had a numerically faster clinical improvement," study authors write in their report. "Significant chest CT improvement, a faster recovery from lymphopenia and favorable side-effect profile in ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population."
Patients treated with ruxolitinib saw a shorter median time to clinical improvement compared to the control group. Researchers reported that 90 percent% of ruxolitinib patients showed CT scan improvement within 14 days, compared with 9 percent of patients from the control group. Three patients in the control group eventually died of respiratory failure. All the severely ill patients who received ruxolitinib survived.
More clinical testing of the drug is needed. A larger Phase III clinical trial RUXCOVID by Incyte and Novartis is now testing up to 400 severely ill COVID-19 patients with the drug, according to Huang. Preliminary clinical data from the study is expected during the summer, he added. "This is the first therapy we know of that appears to work effectively to quiet the cytokine storm and inflammation in severe COVID-19 disease, and there are no significant toxicities to patients who take the drug by two pills a day," Huang said. "This is critical until we can develop and distribute enough effective vaccine to help prevent people from becoming infected."
Calming the 'Cytokine Storm' The so-called cytokine storm that inundates the bodies of severely ill COVID-19 patients with inflammatory cells produced by the immune system is a common feature of children battling secondary HLH, which happens in patients where initial HLH treatment has not worked. Huang, who along with a large portion of the world's scientific community was busy trying to study and find solutions to COVID-19, noticed this common clinical feature of both illnesses.
He also noticed that severe COVID-19 disease clinical manifestations are very similar to those seen in transgenic laboratory mice created to faithfully mimic human secondary HLH in the lab. That preclinical laboratory research, some of it in collaboration with the researchers in Wuhan, China, helped identify the drug ruxolitinib for treating secondary HLH. The anti-inflammatory drug is also used to treat other blood diseases including leukemia.
"I approached our research colleagues in Wuhan and explained our observations and recommended this drug be tested to quiet the cytokine storm in the multi-system inflammation in patients with severe COVID-19 disease," Huang said. "The disease was spreading very rapidly and many people were dying. We believed the existing clinical drug would help save lives. So, we worked to push it forward before there is an effective vaccine for everyone."
Huang said the work with colleagues in China was completed on a compressed timeframe as scientists around the world went on high alert to battle the pandemic in January. During their work, Huang and researchers in China found other clinical studies involving other diseases where ruxolitinib also had worked well at quieting inflammation, and testing on COVID-19 patients proceeded.
Funding support for the JACI study came as part of an Emergency Research Project of Tongji Hospital, Huazhong University of Science and Technology (2020kfyXGYJ045), an Emergency Research Project of Hubei province (2020FCA006). Story Source: Materials provided by Cincinnati Children's Hospital Medical Center. Note: Content may be edited for style and length. Journal Reference:
Yang Cao, Jia Wei, Liang Zou, Tiebin Jiang, Gaoxiang Wang, Liting Chen, Liang Huang, Fankai Meng, Lifang Huang, Na Wang, Xiaoxi Zhou, Hui Luo, Zekai Mao, Xing Chen, Jungang Xie, Jing Liu, Hui Cheng, Jianping Zhao, Gang Huang, Wei Wang, Jianfeng Zhou. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. Journal of Allergy and Clinical Immunology, 2020; DOI: 10.1016/j.jaci.2020.05.019
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Cincinnati Children's Hospital Medical Center. "HLH research points to treatment for COVID-19 cytokine storms: How mice that model immune disease's cytokine storms may point to solution for global pandemic." ScienceDaily. ScienceDaily, 28 May 2020. <www.sciencedaily.com/releases/2020/05/200528092132.htm>.