From trying to understand lung immunity in COVID-19 patients to recognizing the impact the pandemic has had on mental health, researchers at Case Western Reserve University and affiliated health care systems have joined forces to expand and improve research on the virus in the community and beyond.
Case Western Reserve University School of Medicine established a COVID-19 Task Force and the Rapid Response COVID-19 Related Pilot Funding Research Opportunity under the direction of virologist Jonathan Karn and rheumatologist Nora Singer. Since its establishment in March, the task force continues to recruit faculty researchers with diverse backgrounds from across campus and collaborate with university affiliates to conduct multidisciplinary research and develop methods that tackle the different effects of COVID-19.
Karn, professor and chair of the Department of Molecular Biology and Microbiology, said he was impressed with how the initiative has inspired innovative and interdisciplinary collaborative research from across the university and other health systems.
“It is no exaggeration to say that the SARS-CoV-2 pandemic is not only the greatest public health emergency in a century, but it is also creating unprecedented challenges to our economic and social systems,” Karn said. “As a result, our efforts to develop and deliver drugs and vaccines, to study spread of the disease and its impact on different communities, and to understand the impact of the disease on patients and the broader community all benefit from the integrated and multidisciplinary approach that this research task force is catalyzing.”
With support from multiple funding partners across CWRU, the task force awarded over $500,000 in pilot grants to 18 interdisciplinary research teams for the Rapid Response COVID-19 Related Pilot Funding Research Opportunity. On behalf of the COVID Research Task Force, the pilot program was overseen by the Community & Collaboration component of the Clinical and Translational Science Collaborative.
Nearly 50 research teams submitted their project proposals addressing different aspects of the COVID-19 pandemic. The research teams involved faculty from six Case Western Reserve schools and colleges, as well as three health care systems and three other universities.
The awards range from $20,000 to $40,000 each for one year and are meant to “support new research initiatives that will make immediate progress toward reducing harm to individuals, groups, and society from the SARS-CoV-2 and COVID-19 pandemic.”
The Rapid Response COVID-19 Related Pilot Funding Research Opportunity awardees, listed by funding source, are:
NORD Family Foundation
Detection and capture of SARS-CoV-2 virus and antibodies using CAPTIV
Awardee: Susann Brady-Kalnay and Robert Brown (Co-PI)
Department of Molecular Biology and Microbiology, CWRU School of Medicine; Department of Physics, CWRU College of Arts and Sciences
Proposal: “We propose use of a novel device (CAPTIV) for the detection and capture of both the infecting SARS-CoV-2 virus particles and separately the anti-viral human antibodies to provide not only diagnosis of active infection but also collection of antibodies important for demonstrating recovery from the infection using a rapid, low-cost, highly sensitive measurements. The approach utilizes the attachment of magnetic particles to the viral material or antibodies present in biological fluids.”
Lung immunity after COVID-19
Awardee: David Canaday and Richard Silver (Co-PI)
Division of Infectious Diseases, University Hospitals; Division of Pulmonary, Critical Care and Sleep Medicine, CWRU School of Medicine
Proposal: “The rapid spread of the COVID-19 pandemic and its resulting economic disruption have made development of an effective vaccine an urgent global health priority. To facilitate this work, we propose to recruit individuals who have recovered from COVID-19 to participate in research bronchoscopy procedures which will collect lung immune cells.
“Understanding the functions of these cells will clarify which local immune responses must be targeted to prevent respiratory spread of the novel coronavirus.”
Humoral immunity to COVID-19
Awardee: Christopher King (PI)
Division of Experimental Pathology, Department of Pathology, CWRU School of Medicine
Proposal: “The goal of this proposal is to develop a panel of serological assays that will identify the breadth and strength of host immune response to SARSCoV-2 infection with the long-term goal of potentially identifying individuals previously exposed and infected with SARS-CoV-2 in serological surveys, characterize potential biomarkers of protection to subsequent infection and pinpoint individuals with prior COVID-19 with robust antibody responses as potential donors of convalescent plasma.”
Trimeric receptor binding domain of Cov-2 as a multipotential therapeutic agent
Awardee: Paraswaran Ramakrishnan (PI)
Division of Experimental Pathology, Department of Pathology, CWRU School of Medicine
Proposal: “Development of agents that prevent viral entry into cells is a first line treatment for virus infection. We propose to use a laboratory modified fragment of the Cov-2 virus surface protein called spike to competitively block virus infection and to identify antiviral antibodies from recently infected patients.
“This approach offers immediate application for the development of treatments to limit the spread of Cov-2 and to provide assays for the detection of antiviral antibodies in blood.”
Clinical and Translational Science Collaborative
Addressing ethical, social, and regulatory issues in research during the COVID-19 pandemic
Awardee: Daniel Tisch and Aaron Goldenberg (Co-PI)
Departments of Population and Quantitative Health Sciences and Bioethics, CWRU School of Medicine
Proposal: “Research during the COVID-19 raises new ethical, social, and regulatory questions for researchers and participants. Our goal is to advance COVID-19 research ethics through engagement with stakeholders and the creation of regulatory guidance resources to support research during pandemics.
“This project bridges regulatory bodies (IRBs, public health departments, clinical care, and the research community) to promote an ‘ethical and socially grounded’ translational pipeline for COVID research.”
Determining the diagnostic and prognostic value of underlying cutaneous disease and cutaneous eruptions in patients with COVID-19
Awardee: Anthony Fernandez and Christine McDonald (Co-PI)
Department of Inflammation and Immunity, Cleveland Clinic
Proposal: “Skin manifestations of viral illnesses are common, and are sometimes used to identify infection or predict disease outcomes. Since the onset of the COVID-19 pandemic, a variety of rashes in affected patients have been described.
“Given that skin rashes can be easily identified visually and immediately acted upon, this study will define features of COVID-19 skin conditions using patient samples and determine their utility to define disease onset or predict disease outcomes in COVID-19 patients.”
Neighborhood context of social vulnerability and perceptions of COVID-specific risk and prevention
Awardee: Elaine Borawski and Janet McGrath (Co-PI)
Department of Population and Quantitative Health Sciences, CWRU School of Medicine; Department of Anthropology, College of Arts and Sciences
Proposal: “The COVID pandemic has reinforced the importance of location and neighborhood context on health and well-being. Combining neighborhood data and local input, this interdisciplinary project will enhance understanding of the role of place in COVID risk perceptions and behaviors.
“The pilot leverages mixed-methods to create a rich contextualized dataset to better inform public health messaging and interventional efforts to address the disproportionate impacts of COVID among vulnerable neighborhoods.”
Glycemic control and COVID-19 disease severity among patients with chronic kidney disease
Awardee: William Bush (PI)
Department of Population and Quantitative Health Sciences, CWRU School of Medicine
Proposal: “Recent reports suggest that COVID-19 patients who cannot control their blood sugar have worse disease than those with controlled blood sugar. The relationship between blood sugar control and COVID-19 has not been examined in the United States.
“We will examine this relationship in Cleveland patients with chronic kidney disease, many of whom have or are at great risk of developing type 2 diabetes. This study may help physicians predict which patients will need extra care when they have COVID-19.”
COVID-19 associated coagulopathy—developing a Point-of-Care Device for Diagnosis
Awardee: Lalitha Nayak (PI)
Department of Medicine, School of Medicine; Case Comprehensive Cancer Center
Proposal: “COVID-19 portends a high risk for blood clots, a major cause of severe disease and death. While monitoring the coagulation status is crucial, presently used assays take time and a significant amount of blood. Our novel point-of-care device uses miniscule quantities of blood to rapidly assess coagulation abnormalities at the bedside.
“We propose to optimize this device so that it can be used specifically in this unique coagulopathy and guide timely intervention in these critically ill patients.”
Swetland Center for Environmental Health and the Clinical and Translational Science Collaborative (co-sponsor)
Understanding the behaviors of dental aerosol flume and engineering effective capture system for COVID-19 risk mitigation
Awardee: Bill Yuand Fabio Piola Rizzante (Co-PI)
Department of Civil and Environmental Engineering, Case School of Engineering; Department of Comprehensive Care, CWRU School of Medicine
Proposal: “Dental treatment procedures produce high-speed dental aerosols, which can carry COVID-19 and possess a major threat to the health of dentists, staff and patients. This collaboration involving engineers and dental clinician will conduct pilot study to understand the behaviors of dental aerosol flume and its interactions with engineered surfaces.
“From these, solutions will be developed to effective capture and sanitize dental aerosols and mitigate the risk of COVID-19 at dental clinics.”
Digestive Health Research Institute
Impact of COVID-19 on alcohol related liver disease
Awardee: Srinivasan Dasarathy (PI)
Department of Gastroenterology, Hepatology & Nutrition
Proposal: “Clinical outcomes are worse in patients with COVID-19 who have underlying comorbidities. Alcohol use disorders (AUD) and alcohol-related liver disease (ALD) increase susceptibility to infections but there is no data on the impact of COVID19 in patients with ALD and AUD.
“Social distancing was associated with increased alcohol sales based on marketing reports and is likely to contribute to increased frequency and severity of AUD and ALD. These will be evaluated in the proposed studies.”
Case Comprehensive Cancer Center
COVID-19 immune response and burden of disease with and without cancer
Awardee: Nora Singer and Jonathan Karn (Co-PI)
Department of Rheumatology, MetroHealth Medical Center; Department of Molecular Biology and Microbiology, CWRU School of Medicine
Proposal: “In this study, we will compare patients with lymphomas, myeloma, and related conditions who don’t need cancer medicines or are in remission who have also been diagnosed with COVID-19 to see how well the T-cell arm of their immune system works against COVID-19/CoV2. Whether patients with blood cancers or precancerous conditions can make protective T-cell responses to COVID-19 will be tested.
“We will also use patient reported outcomes to measure the impact of COVID-19 disease in cancer patients.”
Preventive behaviors, care experience, and health outcomes of underserved cancer patients during the COVID-19 pandemic
Awardee: Amy Zhang and Siran Koroukian (Co-PI)
CWRU School of Nursing; Department of Population and Quantitative Health Sciences, CWRU School of Medicine
Proposal: “Cancer patients are at higher risk for severe illnesses caused by COVID-19. African American and rural cancer patients are particularly vulnerable because they have limited socioeconomic resources and access to health care.
“We seek to conduct a survey study to understand how they protect themselves and home, what helps or hinder their prevention effort, experience of cancer and health care disruption, socioeconomic unmet needs, and the impact of these factors on their health during the pandemic.”
Cleveland Brain Health Initiative
Risk and protective factors for lasting mental health impact of the COVID-19 pandemic
Awardee: Joel Hughes (PI)
Department of Psychological Sciences, Kent State University
Proposal: “The COVID-19 pandemic is expected to cause psychological distress. During the spring of 2020 we found high levels of distress among college students, a vulnerable population.
“However, people are resilient, and distress may be temporary or lasting. Also, we do not know what increases risk or protects against mental health problems from COVID-19.
“This research will provide a 6-month follow-up of mental health outcomes, and will identify protective and risk factors for depression and anxiety.”
NSC-based investigation of the role of glia in SARS-CoV2 neurovirulence
Awardee: William Lynch (PI)
Brain Health Research Institute, Kent State University, Northeast Ohio Medical University
Proposal: “Multiple clinical reports have documented neurological symptoms in a large cohort of COVID-19 patients. While prior work on other human and animal coronaviruses indicate they can infect the CNS, damage cells and cause severe neurological manifestations, the molecular mechanisms remain largely unresolved.
“This grant will use engineered stem cells and mouse brain chimeras to understand how SARS-CoV-2 structural elements interact with neural cells and induce neuropathologic sequelae in vivo.”
COVID-19 Pandemic, Social Inequalities, and Mental Health
Awardee: Megan Holmes and Robin Rentrope (Co-PI)
CWRU Jack, Joseph and Morton Mandel School of Applied Social Sciences; CWRU Frances Payne Bolton School of Nursing
Proposal: “There is rising concern that the COVID-19 pandemic could inflict long-lasting mental health problems on an unprecedented global scale. Social determinants of health (e.g., poverty, physical environment, race) can also affect COVID-19 outcomes, including mental health.
“This goal of this study is to better understand the effect of COVID-19 pandemic on mental health, identify coping strategies used to reduce stress, and examine the relations between social inequalities, COVID-19, and mental health.”
Center for AIDS Research
Impact on the GI tract from the triple action of HIV, SARS-CoV-2, and opioid use
Awardee: Alan Levine (PI)
Department of Molecular Biology and Microbiology, CWRU School of Medicine
Proposal: “The gastrointestinal (GI) tract is a target for HIV, opioid use, and SARS-CoV-2, in that these individuals experience a variety of GI symptoms that include constipation, diarrhea, nausea, vomiting, and/or abdominal discomfort. When a person with HIV who uses opioids is infected by SARS-CoV-2, the integrity of the gut wall is damaged due to the triple threat of opioid use and viral infection.
“We will define how the gut is harmed by the combined effects of SARS-CoV-2 infection and opioid use.”
Regulation of SARS-CoV-2 receptors using long non-coding RNAs
Awardee: Saba Valadkhan (PI)
Department of Molecular Biology and Microbiology, CWRU School of Medicine
Proposal: “The proposed research aims to use a new class of therapeutics, antisense therapies, for reducing the level of three molecules that act as receptors for SARS-CoV-2 and thus, enable the virus to infect human cells. All three molecules are present in cells that line the human airways and so can enable the respiratory infection caused by SARS-CoV-2.
“In addition, two of the molecules are present in lymphocytes and may protect these cells from massive death in coronavirus-infected individuals.”