Highlights from UAMS' COVID-19 Response
Transmission – Preventing and understanding how the coronavirus spreads
ACE2 to Predict Outcomes in Infection with SARS-CoV-2 - John Arthur, M.D., Ph.D. Laura James, M.D. COVID-19 severity ranges from asymptomatic to deadly, but currently there is no way to predict which patients infected with SARS-CoV-2 will develop severe symptoms. Arthur and his team are investigating approaches to accurately make this prediction on the basis of specific features of proteins and DNA in the blood of individual patients. Identifying patients at highest risk of severe disease could save lives by designating the appropriate treatment at an early stage.
Sprayable Plant-based Surface Coatings Target the COVID-19 Virus - Peter Crooks, PhD, Jamie Hestekin, PhD, and Christa Hestekin, PhD. Crooks at UAMS and colleagues at the University of Arkansas at Fayetteville have developed a sprayable surface coating that quickly destroys viruses. Using a plant-based nanomaterial, they have developed coatings that kill bacteria by attaching molecules that also kill viruses like COVID-19. A durable product applied to frequently touched objects like door knobs and packaging will be critical to reducing coronavirus spread. See the full research abstract.
Novel Intubating Frame to Reduce Contamination in COVID-19 Patients - Faiza A. Khan, MD, Zachary B. Lewis, MD, Sina B. Ekici, MD and Nadir Sharawi, MBBS. Aerosol generating procedures (e.g., intubation/extubation), pose significant risk to health care providers. Several devices or barrier enclosures (e.g., aerosol box and face tent) have been created/modified to minimize risk. However, limitations such as restricted hand movement makes simulated intubation scenarios difficult. A UAMS emergency medicine team devised a novel, reusable and easy-to-assemble PVC frame with HEPA filter and suction port that facilitates virus particle removal.
Treatment – Finding ways to treat those infected
UAMS Receives FDA Authorization for State-wide Convalescent Plasma Use - Tina S. Ipe, MD, MPH. This authorization ensures that convalescent plasma collected in Arkansas will benefit Arkansas patients through a statewide convalescent plasma effort. This program provides the ability to explore potential treatment in Arkansas. COVID-19 convalescent plasma (CCP) is the blood component collected from people who have recovered from COVID-19, the illness caused by the new coronavirus. The plasma contains antibodies that can help fight infection. UAMS is teaming up with other Arkansas hospitals in the state to treat the sickest and the most vulnerable patients. Learn more
Developing Reagents to Enable Antibody-mediated Antiviral Therapies Against COVID-19 (DREAM ATAC) - Craig Forrest, PhD, Karl Boehme, PhD, Joshua Kennedy, PhD. Forrest teamed with Drs. Karl Boehme and Joshua Kennedy to investigate immune system antibodies produced in response to SARS-CoV-2. They are analyzing antibodies in blood serum (donated by people who have recovered from COVID-19) to be used as an emergency treatment. The results are used to identify potential donors for antibody treatment. The team will also determine the percentage of people in the population with antibodies against the virus, helping to define the epidemiology of COVID-19 in Arkansas. Learn more
A Radiation Mitigator as a Potential Treatment for COVID-19 - Robert J. Griffin, Nukhet Aykin-Burns, Michael Borrelli, and Peter M Corry. The Corry/Griffin research groups used FDA approved antioxidant N-acetylcysteine (NAC) as a radiation mitigant and to block vascular shutdown. Briefly, 62% of mice were rescued from a lethal 20 Gy dose of ionizing radiation, localized to the abdomen, by the administration of NAC up to four hours post irradiation. Moreover, NAC was able to blunt/eliminate the adhesion molecule induction associated with vascular shutdown/hypoxemia. Cytokine storms are involved in COVID-19 critical patients and NAC treatment has the potential to reduce mechanical ventilation and mortality.
SARS-CoV-2 Cross-protection Study using Surrogate Coronavirus and Recombinant Proteins - Marli P. Azevedo, PhD; Lisa Mullis; Bruce Erickson, PhD; Kuppan Gokulan, PhD; Sangeeta Khare, PhD and R. Doug Wagner, PhD. Antibody-Dependent Enhancement (ADE) has been reported to occur during SARS-CoV infection and likely SARS-CoV-2. Therefore, successful vaccines depend on the role of the S protein in ADE and examining alternative solutions (e.g., select epitopes for a vaccine target). By generating recombinant SARS-CoV-2 and NL63 Spike proteins in a baculovirus system, generate polyclonal antibodies against the rS were made. We have identified epitope peptides from the spike protein and will select antigenic epitopes capable of inducing neutralizing antibodies to prevent viral entry/infection, screening to avoid ADE.
Can Oxygen Carrier Molecules Offer Neuroprotection in Oxygen deficient Conditions such as During Severe COVID-19-induced Pneumonia? - Abdallah Hayar, PhD. Prolonged hypoxia due to lung infection by SARS-CoV-2 can disrupt synaptic transmission and cause neuronal cell death. This can disrupt the brain’s ability to coordinate breathing/heart rate thus augmenting multiple organ failure and death. Mechanical ventilation, an essential tool in ICU care of COVID-19 patients, can overstretch the lungs and cause lung injury/inflammation. Several perfluorocarbons can carry oxygen and may be used to treat hypoxic COVID-19 patients. In particular, DDFPe is safe to treat acute ischemic stroke patients. Whether DDFPe improves oxygen exchange in a mouse model and/or has neuroprotective effects on brainstem cardiorespiratory neurons is being investigated. If positive, DDFPe may improve oxygenation in COVID-19 patients.
Development of a High-density Protein Array for COVID-19 Antibody Binding Assays - Visanu Wanchai, PhD, Søren Brunak, PhD, David Hirschberg, PhD, and David Ussery, PhD. Viruses have limited genome sizes, but can encode many proteins, taking advantage of multiple reading frames, mRNA editing, and alternative splicing. A high density protein array, containing 4 million probes (16mer peptides) from a set of several thousand genomes from the coronavirus family was designed. These high density arrays will be probed by antibodies from sera from ~1,000 COVID-19 positive patients (Washington state) and frozen blood sera for the control set. We anticipate finding strong epitopes for designing COVID-19 specific antibodies with little cross reactivity with other coronaviruses.
AR-Connect – Mental Health Services - Teresa Hudson, PhD. Easy access to substance abuse and mental health care is important, but particularly urgent during the COVID-19 pandemic. The UAMS Psychiatric Research Institute, partnered with the Arkansas Department of Human Services’ Division of Aging, Adult, and Behavioral Health Services has created AR-Connect, a 24/7 behavioral health call center. AR-Connect provides care to all Arkansans dealing with a variety of mental-health issues, from substance abuse disorders to mental illnesses ranging from anxiety/depression to bipolar disorder/schizophrenia. AR-Connect helps Arkansans get immediate assistance and eventually connects them with treatment options in their local area. AR Connect resides within the Institute for Digital Health & Innovation’s telehealth platform.
Prevention – Stopping COVID-19 before it can take hold
A Lung Model for Studying COVID-19 Pathogenesis and Antiviral Drug Discovery - Xuming Zhang, PhD and Roger Pechous, PhD. Zhang, Pechous, and their team are investigating the impact of COVID-19 on the respiratory tract and assisting health care professionals in understanding disease progression. With a human lung tissue model that mirrors normal lung function, the team will determine the cell types infected by the virus, their pathological changes, and immune response to the infection. This research will also examine candidate drugs that are known to be effective against other coronaviruses.
Identification of Compounds to Inhibit SARS-Cov-2 - Kevin Raney, PhD and Peter Crooks, PhD. Working together, the Raney and Crooks labs are pursuing therapies that prevent the COVID-19 virus from replicating. The enzymes responsible for viral replication provide the best targets for developing new therapies. Using sophisticated computer simulation and a library of compounds, they will identify potential enzymes for new highly specific antiviral therapies.
PCORI - Impact of COVID-19 Outbreak on Minority Health and Health Disparities - Pearl McElfish, PhD. Minority communities, such as Pacific Islanders in Northwest Arkansas, are disproportionately affected by COVID-19. Pearl McElfish, PhD and her team compare the effectiveness of preventive interventions for minority communities to ultimately reduce the disparities caused by COVID-19. As a supplement to an existing PCORI award, the team will conduct a mixed-methods concurrent triangulation study to increase knowledge of COVID-19 risk exposure in Pacific Islanders, community members’ knowledge of preventive recommendations, and barriers/facilitators to prevention and COVID-19 testing. Pacific Islander community members will complete an extensive 48-item survey with 40 participants chosen randomly to complete an in-depth qualitative interview.
Epidemiology – Understanding how the coronavirus is spreading
Exploratory Analysis of Social Network Messages - Chenghui Li, PhD. Li and her team are exploring social network messages to understand public attitudes/behaviors during the COVID-19 outbreak. Analyzing online conversations could help public health officials respond to and understand the dynamics of information/misinformation spread about the pandemic. The group will apply state-of-the-art artificial intelligence and data collection techniques to Twitter to characterize public understanding about COVID-19.
Detection of Covid-19 from a Wastewater Treatment Plant in Conway, Arkansas -Catherine Shoults, Tom Powell, PhD, Jing Jin, PhD, Mohammed Orloff, PhD, David Hirschberg, PhD, and Dave Ussery, PhD. The SARS-CoV-2 genome (shed in feces) has been detected in hospital and community wastewater. In fact, several U.S. communities are being monitored for COVID-19 presence in wastewater treatment plant sludge samples. Two sludge samples were assayed from a Conway, Arkansas wastewater treatment plant for the COVID-19 genome. Estimates of community infection were compared to individual testing, (e.g., rRT-PCR and antibody studies).
Community / Health Disparity – Combatting COVID-19 in Communities
Consumer Health Information on COVID-19 Not Ideally Readable or Actionable - B. Alison Caballero, MPH, CHES; Katherine J. Leath, MPH, MA; and Jamie C. Watson, PhD. Similarities exist between populations at risk for severe COVID-19 and populations at risk for limited health literacy. Because individual behaviors impact disease spread, educational materials must be easy to read/understand, especially in high-risk groups. Online COVID-19 materials were measured for readability, understandability, and actionability with readability formulas and a Patient Education Materials Assessment Tool. Mean readability scores were at a high school reading level and plain language techniques for optimal understanding/action were often missing. Given health literacy limitations for those at high risk for severe COVID-19, clear communications are essential. COVID-19 health education in vulnerable populations must follow plain language guidelines and be tested prior to use.
The Impact of COVID-19 on the Mental Health of High-Risk Populations - PCORI - Keneshia Bryant, PhD. The general population is likely to experience anxiety, depression, stress, and other mental health disorders related to the COVID-19 pandemic. However, people with a history of mental illness and/or substance abuse, those who are incarcerated, and frontline health care and essential workers are at even greater risk for these disorders. Bryant’s team consulted multiple stakeholder groups to establish the COVID-19 Emotional Wellness Task Force and develop a COVID-19 Emotional Wellness research agenda with the long-term goal of supporting those at greatest risk of experiencing a mental health crisis due to the pandemic.