Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&sort=-award_amount
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-award_amount", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=-award_amount", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=-award_amount", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=-award_amount" }, "data": [ { "type": "Grant", "id": "7937", "attributes": { "award_id": "1IK6BX005962-01", "title": "BLR&D Research Career Scientist Application", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-04-01", "end_date": "2027-03-31", "award_amount": null, "principal_investigator": { "id": 23807, "first_name": "Todd A", "last_name": "Wyatt", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1645, "ror": "", "name": "OMAHA VA MEDICAL CENTER", "address": "", "city": "", "state": "NE", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1645, "ror": "", "name": "OMAHA VA MEDICAL CENTER", "address": "", "city": "", "state": "NE", "zip": "", "country": "United States", "approved": true }, "abstract": "My primary research interests address chronic inflammatory lung disease, and the impact that behavioral and environmental exposures play in the compromise of lung innate defense against pathologic lung infections and injury. Utilizing pre-clinical mouse models and state-of-the-art molecular, biochemical, and cellular approaches, I collaborate closely with pulmonologists who practice at the VA to conduct relevant pre-clinical research that can be used to address current clinical concerns. I translate my findings to Veterans’ health using a well- characterized human lung cell and tissue biobank obtained from our lung transplant program. We have an existing cohort of Veterans with rural/agricultural occupational exposures to conduct relevant studies to our service region. There are 3 major research projects currently underway that impact veterans’ health: Malondialdehyde-acetaldehyde adducts and lung injury. Alcohol abuse causing increased susceptibility to pneumonia has been known for over 200 years. Because the majority (>90%) individuals misusing alcohol smoke cigarettes, we study the combination lung injury effects of both cigarettes and alcohol. We identified that the lungs represent a unique environment for the formation of stable malondialdehyde-acetaldehyde protein adducts (MAA adducts), but only under conditions of combined cigarette smoke and alcohol exposure. These MAA adducts cause airway epithelial cell cilia slowing and impair the innate pathogen clearance from the lung. Surfactant protein D (SPD) is a major lung protein that gets adducted when lung aldehyde concentrations are elevated during combined smoke and alcohol exposure and SPD-MAA adducts are detected in the lung only in drinkers who also smoke, leading to alterations in innate lung defense. (Funded by BX003635). Veterans- centric COVID-19 research. The pathogenesis of the SARS-CoV-2 virus and clinical outcomes from COVID 19 are far worse in individuals with certain pre-existing conditions and those of advanced age. It is essential to the health of Veterans to fully define which at-risk conditions particularly impact them and their unique needs to empower clinical preventive care during this and future viral pandemics. Old age and alcohol misuse are associated with cilia dysfunction. SPD has been documented to specifically bind to and neutralize the Spike protein of coronavirus. We hypothesize that altered innate lung defense at the level of mucociliary clearance, anti-microbial surfactants, and viral receptor function will negatively impact susceptibility and pathogenesis of SARS-CoV-2, placing Veterans particularly in harm’s way. We are currently identifying differences in SARS- CoV-2 infection responses between normal airway epithelium and lung macrophages and those cells collected from individuals with COPD, with alcohol use disorder, or of old age. Defining the modalities of risk will empower clinicians to make informed clinical preventive care decisions for Veterans (Funded by BX005413). Agricultural organic dust-mediated lung injury. VISN 23 encompasses a region responsible for the largest agricultural output in the nation. In collaboration with Omaha VA physician scientists, we have built a cohort of Veterans with agricultural exposures to explore the impact of organic dusts on chronic lung inflammatory injury. Using established mouse models, we have identified the therapeutic impact of IL-10 on lung repair from dust- mediated injury. We are currently defining the mechanisms of action through an active NIOSH R01 study and the Central States Center for Agricultural safety and Health (Funded by OH010162). With these innovative research programs, I have been able to provide training and mentoring to many undergraduates, graduate students, fellows, junior scientists and physicians at the Omaha VAMC and affiliated University of Nebraska Medical Center (UNMC). Our efforts to investigate the underlying mechanisms and identify targets for pulmonary disease have brought together physician scientists and basic scientists at the Omaha VA medical center and UNMC, which has led to the development of a VA-funded live-animal microCT Core facility, which I supervise and is the only such instrument in Omaha.", "keywords": [ "2019-nCoV", "Acetaldehyde", "Address", "Admission activity", "Age", "Agriculture", "Alcohol abuse", "Alcohol consumption", "Alcohols", "Aldehydes", "Animal Model", "Animals", "Area", "Award", "Bacterial Infections", "Behavioral", "Binding", "Biochemical", "Biological Markers", "COVID-19", "Caring", "Cells", "Chronic", "Chronic Obstructive Pulmonary Disease", "Chronic lung disease", "Cigarette", "Cilia", "Clinical", "Collaborations", "Core Facility", "Coronavirus spike protein", "Cyclic AMP-Dependent Protein Kinases", "Development", "Dust", "Elderly", "Environment", "Environmental Exposure", "Epithelial Cells", "Exposure to", "Extramural Activities", "Functional disorder", "Funding", "Future", "Grant", "Health", "Health Care Costs", "Healthcare", "Healthcare Systems", "Heavy Drinking", "Hospitals", "Human", "Impairment", "Individual", "Inflammation", "Inflammatory", "Injury", "Interleukin-10", "Laboratories", "Life", "Lung", "Lung Transplantation", "Lung diseases", "Lung infections", "Malondialdehyde", "Manuscripts", "Mediating", "Medical center", "Mentors", "Methodology", "Military Personnel", "Modality", "Molecular", "Morbidity - disease rate", "Mucociliary Clearance", "Natural Immunity", "Nebraska", "Occupational Exposure", "Outcome", "Output", "Pathogenesis", "Pathologic", "Peer Review", "Physicians", "Play", "Pneumonia", "Predisposition", "Preventive care", "Proteins", "Pulmonary Surfactant-Associated Protein D", "Recording of previous events", "Regulation", "Research", "Research Project Grants", "Respiratory Syncytial Virus Infections", "Risk", "Role", "Rural", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Safety", "Sampling", "Savings", "Science", "Scientist", "Seminal", "Services", "Smoke", "Smoker", "Smoking", "Source", "Substance abuse problem", "Supervision", "System", "TNF-alpha converting enzyme", "Therapeutic", "Time", "Tissues", "Training", "Translating", "Universities", "Veterans", "Viral", "Virus", "Virus Diseases", "Virus Receptors", "Work", "adduct", "agricultural center", "airway epithelium", "airway inflammation", "alcohol exposure", "alcohol misuse", "alcohol response", "alcohol use disorder", "antimicrobial", "biobank", "career", "cell motility", "chronic inflammatory lung disease", "cigarette smoke", "cohort", "cost", "desensitization", "digital", "disorder risk", "experience", "exposure to cigarette smoke", "former smoker", "graduate student", "human old age (65+)", "improved" ], "approved": true } }, { "type": "Grant", "id": "7944", "attributes": { "award_id": "1I01HX003364-01A1", "title": "Dissemination and Implementation of a Videoconference Antimicrobial Stewardship Team (VAST)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-05-01", "end_date": "2026-04-30", "award_amount": null, "principal_investigator": { "id": 23816, "first_name": "CHARLESNIKA T", "last_name": "EVANS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1483, "ror": "https://ror.org/01vrybr67", "name": "Louis Stokes Cleveland VA Medical Center", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23817, "first_name": "Robin", "last_name": "Jump", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1483, "ror": "https://ror.org/01vrybr67", "name": "Louis Stokes Cleveland VA Medical Center", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Antimicrobial stewardship guidelines call for a multidisciplinary team with an infectious disease (ID) physician and ID-trained clinical pharmacist as core members. Unfortunately, there are insufficient ID- trained specialists to staff on-site antimicrobial stewardship programs throughout VA. Significance: This proposal is highly significant for Veterans and the goals of VA. Veterans experience many of the risk factors associated with development of antimicrobial resistant and healthcare-associated infections. The unprecedented effects of the novel Coronavirus disease 2019 (COVID-19) on the health of our Veterans and on our entire healthcare system makes the demand for ID expertise even more apparent, especially in long-term care. Also, this study directly addresses the VA MISSION ACT to improve access to care, timeliness and quality of care, using telehealth services. Finally, this project is aligned with the priorities of our operation partners: VA Antimicrobial Stewardship Taskforce (ASTF), the VA National Infectious Disease Service (NIDS), VA Pharmacy Benefits Management (PBM) Services, and the Office of Rural Health. Innovation and Impact: The design is innovative because we will systematically test and assess implementation barriers to telehealth for antimicrobial stewardship, a novel approach that has not been implemented in VA facilities, other than in our previous pilot study. Further, the Antibiotic Use Reports (AURs) are an innovative adaptation of peer-comparison, an antibiotic stewardship strategy successful in outpatient settings. This project will provide findings for a scalable model that could be deployed nationally to all applicable VAMCs, continuing the role of VHA as a leader in implementing large-scale interventions focused on prevention and management of ID and stewardship. Specific Aims: Our goal is to implement a multidisciplinary videoconference antimicrobial stewardship team (VAST) in VAMCs using SCAN-ECHO. Our central hypothesis is that feedback reports that quantify facility- level antibiotic use will enhance the efficacy of VASTs to support antimicrobial stewardship. We propose a Type 2 hybrid effectiveness-implementation design, comparing clinical effectiveness in sites that implement the VAST alone (VAST-) to sites that implement the VAST augmented by facility-level Antibiotic Use Reports (VAST+). Aims are: 1) Identify and test effective strategies for implementing the VAST; 2) Determine the influence of the VAST overall and VAST+ on the care of Veterans with suspected infections; 3) Determine the influence of the VAST overall and VAST+ on antibiotic use at each VAMC. Methodology: We will randomize rural VAMCs that do not have ID-trained professionals on staff to implement the VAST alone (VAST-) versus VAST + antibiotic use feedback (VAST+). Aim 1: We will assess modification and adaptations at the intervention sites and by the infectious disease experts. Methods will include process maps and semi-structured interviews to gather qualitative data about what key VAST members perceive as facilitators, barriers and burden to VAST implementation. We will also evaluate costs of implementation. Aim 2: We will evaluate the Veteran population served, clinical activities, and user perceptions of the VAST. We will assess the concordance of clinical care with recommendations from evidence-based clinical practice guidelines. VAST members’ perceptions of the quality and timeliness of care will be evaluated. Aim 3: The primary outcome measure will be overall rates of antibiotic use. Secondary outcomes will be changes in the rates of broad-spectrum antibiotic use, antibiotic starts, and length of antibiotic therapy. Next steps/Implementation: Testing effective implementation of the VAST at additional VAMCs is an important step toward augmenting antimicrobial stewardship in both acute- and long-term care settings. In collaboration with VA clinical operation partners, outcomes from this trial will be used to roll-out an implementation playbook to be used by other VAMCs, as well as non-VA settings.", "keywords": [ "Acute", "Address", "Administrator", "Affect", "Antibiotic Therapy", "Antibiotics", "Antimicrobial Resistance", "Area", "COVID-19", "Caring", "Cellulitis", "Cessation of life", "Clinical", "Clinical Nurse Specialists", "Clinical Pharmacists", "Clinical Practice Guideline", "Clinical effectiveness", "Collaborations", "Communicable Diseases", "Community Healthcare", "Complex", "Consultations", "Data", "Development", "Dissemination and Implementation", "Effectiveness", "Evidence based intervention", "Feedback", "Goals", "Guidelines", "Health", "Health Services Accessibility", "Healthcare", "Healthcare Systems", "Improve Access", "Individual", "Infection", "Infection Control", "Intervention", "Interview", "Length", "Long-Term Care", "Maps", "Measures", "Medical center", "Mentors", "Methodology", "Methods", "Modeling", "Modification", "Outcome", "Outcome Measure", "Outpatients", "Participant", "Patient Care", "Perception", "Pharmacists", "Physicians", "Pilot Projects", "Pneumonia", "Policy Maker", "Prevention", "Process", "Provider", "Quality of Care", "Randomized", "Recommendation", "Reporting", "Resources", "Risk Factors", "Role", "Rural", "Rural Health", "Services", "Site", "Specialist", "Structure", "System", "Testing", "Time", "Training", "United States Department of Veterans Affairs", "Urinary tract infection", "Veterans", "Work", "antimicrobial", "base", "care outcomes", "care providers", "clinical care", "combat", "design", "effectiveness implementation design", "effectiveness implementation study", "evidence base", "evidence based guidelines", "experience", "feasibility testing", "geographically distant", "global health", "healthcare-associated infections", "implementation barriers", "implementation cost", "implementation evaluation", "improved", "innovation", "interest", "medical specialties", "member", "military veteran", "multidisciplinary", "novel coronavirus", "novel strategies", "operation", "pathogen", "patient safety", "patient subsets", "peer", "pharmacy benefit", "prevent", "primary outcome", "programs", "secondary outcome", "telehealth" ], "approved": true } }, { "type": "Grant", "id": "7971", "attributes": { "award_id": "1I01HX003277-01A1", "title": "Hospital In Home: Evaluating Need and Readiness for Implementation (HENRI)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-06-01", "end_date": "2026-05-31", "award_amount": null, "principal_investigator": { "id": 23857, "first_name": "William W.,MPH, MD", "last_name": "Hung", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1653, "ror": "", "name": "VETERANS AFFAIRS, UNITED STATES DEPARTMENT OF", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23858, "first_name": "ORNA K.", "last_name": "INTRATOR", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 23859, "first_name": "Jennifer L", "last_name": "Sullivan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1653, "ror": "", "name": "VETERANS AFFAIRS, UNITED STATES DEPARTMENT OF", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: The Department of Veterans Affairs (VA's) Hospital In Home (HIH) program, designed from experiences of the Hospital At Home community program, is a model of care that delivers patient-centered, acute-level hospital care at home which has demonstrated safety, effectiveness and patient satisfaction beyond those observed in hospitals. Since 2010, the VHA Office of Geriatrics & Extended Care (GEC), through its transformational programs and mentored partnerships has spurred the development of [12] HIH program sites nationally, which have all been sustained by their parent station. Significance/Impact: [Hospital In Home is a mix of interventions and levels of implementations; understanding how to weave these successfully is the overarching aim of this project.] Continued spread of HIH across the VA requires evidence be established regarding the need for HIH and about the implementation of existing HIH programs. Understanding barriers and facilitators and processes of implementation of HIH programs will allow more facile adoption of HIH programs allowing for substantial cost savings of about $3,000 per inpatient event. Especially in the era of the Mission Act, having HIH available may incentivize Veterans to choose VA. [With the recent Covid-19 pandemic, HIH has been identified as a potential contributor to addressing the disease and sequelae.] Innovation: This project will generate generalizable knowledge regarding implementation of HIH models and will advance implementation science from its application of implementation science frameworks, Re-Aim- PRISM and novel methods such as Implementation Mapping. The project will curate knowledge garnered from the existing programs and develop tools to disseminate it. It will develop and conduct readiness for implementation surveys. Finally, it will “dry-run” implementations in sites with greater readiness for implementation. The results of the “dry runs” will provide feedback to the implementation planning thus increasing their probability of successful adoption of HIH and its sustainment and growth. Specific Aims: 1. Establish evidence regarding the implementation of the existing HIH sites using a mixed methods approach. Deliverables: An evaluation framework and report summarizing the experiences of the existing sites. 2. Develop operational implementation tools and a readiness for implementation survey to be conducted. Deliverables: A survey of readiness for implementation and prioritization of sites ready to implement; implementation tools. 3. Select ten new sites with the greatest evidence of readiness for implementation to conduct “dry-runs” and create blueprints for implementation; identify causal loop diagram(s); catalog the evidence. Deliverables: Report summarizing common and site specific implementation themes; Site-specific Implementation logic models; Searchable catalog of HIH implementation strategies. Methodology: This mixed-methods project will conduct quantitative analyses, interviews, focus groups and “dry runs” applying implementation science frameworks and methods (RE-AIM-PRISM, implementation mapping) and system science to understand the existing HIH programs and to create implementation tools, evaluation framework, readiness survey, causal loop diagrams and a searchable catalog of HIH implementation evidence. Implementation/Next Steps: Future work will develop simulation studies and conduct evaluations of newly implemented sites as well as a hybrid II implementation trial of the effectiveness and safety of the HIH model.", "keywords": [ "Accident and Emergency department", "Acute", "Address", "Admission activity", "Adoption", "Beds", "Benchmarking", "COVID-19 pandemic", "Caring", "Catalogs", "Client satisfaction", "Communities", "Complex", "Contracts", "Cost Savings", "Development", "Disease", "Effectiveness", "Evaluation", "Evaluation Reports", "Event", "Feedback", "Focus Groups", "Future", "Geriatrics", "Growth", "Health Services Accessibility", "Home", "Hospital safety", "Hospitals", "Hybrids", "Implementation readiness", "Incentives", "Inpatients", "Intervention", "Interview", "Knowledge", "Learning", "Logic", "Long-Term Care", "Mentors", "Methodology", "Methods", "Mission", "Modeling", "Parents", "Patient-Focused Outcomes", "Probability", "Process", "Quality of Care", "Quantitative Evaluations", "Reach Effectiveness Adoption Implementation and Maintenance", "Readiness", "Reporting", "Resources", "Running", "Safety", "Science", "Series", "Site", "Standardization", "Surveys", "System", "Techniques", "United States Department of Veterans Affairs", "Variant", "Veterans", "Work", "base", "design", "effectiveness implementation trial", "experience", "experimental study", "guidebooks", "implementation barriers", "implementation evaluation", "implementation framework", "implementation science", "implementation strategy", "implementation tool", "informant", "innovation", "interest", "novel", "patient oriented", "preference", "programs", "simulation", "stem", "tool" ], "approved": true } }, { "type": "Grant", "id": "7985", "attributes": { "award_id": "1I01RX003622-01A2", "title": "Exercise-based Program for Rehabilitation of Veterans with Severe Mental Illness", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-06-01", "end_date": "2026-05-31", "award_amount": null, "principal_investigator": { "id": 23883, "first_name": "GRETCHEN L", "last_name": "HAAS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23884, "first_name": "Vishwajit Laxmikant", "last_name": "Nimgaonkar", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "This is a Hybrid 1, effectiveness-implementation study of yoga-based exercise (YE) as an adjunctive tool for rehabilitation among persons with Severe Mental Illness (SMI), defined here as schizophrenia (SZ), schizoaffective disorder (SZA) and bipolar I disorder (BP1). SMIs are common, severe and devastating conditions that cause enormous disability world-wide. Many features of SMI can be treated effectively, yet the long-term outcome has not improved much over the past century. The lack of improvement may be due to ineffective treatment of functional deficits in SMI patients, particularly in terms of community functioning, defined here as social, leisure, employment, and life skills functioning in the community. Complementary and Integrative Medicine (CIM) therapies that improve community functions are thus of great interest for treating Veterans with SMI and thereby target an area of high priority for the VA. Prior studies have shown short-term benefits of YE for improving cognitive deficits and community functions among persons with SMI. While the published studies are encouraging, the longer-term benefits of YE are untested, particularly for community functioning. The profile of Veterans with SMI who will accept and adopt YE is also unknown. We have conducted pilot studies and a randomized controlled trial (RCT) for individuals with SMI in India using short-term, simplified YE combined with medications. Recently, we also concluded RELIEVE, a RCT of adjunctive YE for Veterans with post-traumatic stress disorder (PTSD) in the USA (VA RR&D Merit award, PI: L Davis, PsyD). We found encouraging improvements from all our studies, but our Indian and US YE protocols are impractical for Veterans with SMI. For example, some postures may be difficult for older Veterans with amotivation and/or physical disabilities. Therefore, in Aim 1, we will design and evaluate adaptations of the Indian and US YE protocols in a non-religious context (mindfulness, stretching, toning and breathing exercises). We will consult our Indian and US colleagues, our Veterans with SMI and their VA therapists to adapt the protocol for our SMI population. We will also adapt our control condition, the Wellness Lifestyle Program (WLP), from our recently completed RELIEVE study. In Aim 2, we will conduct a 2-armed RCT in which consenting Veterans with SMI will be randomly assigned to one of 2 arms: YE and treatment as usual (TAU, any prescribed treatment) or WLP+ TAU. Unlike prior short-term YE RCTs, the two arms will continue 12 months, including an initial 12-week training period consisting of two supervised sessions per week, followed by a 12-week training period consisting of one supervised session per week, and monthly refresher training sessions offered for the remaining 6 months. We will conform to all COVID-19 related requirements for YE and WLP. Our Hybrid 1 trial will compare the efficacy of YE versus WLP. Primary outcomes are self-report and performance-based measures of community functioning; secondary outcomes are cognition and physical fitness measures. Our goals in Aim 3 are to understand demographic/clinical features of Veterans with SMI who are more likely to accept and adopt YE to enable long-term rehabilitation, by analysis of the RCT data (Aim 3A). We will also conduct qualitative interviews with Veterans who have SMI and participated in the YE intervention arm, referring clinicians, and the Yoga instructor to identify barriers and facilitators for implementation (Aim 3B). The project thus aims to advance our long-term goals for improving the quality of life for Veterans with SMI and to provide evidence to guide home- based and over the longer term, community-based YE practice, consistent with the Mission Act and the VA Strategic Plan. Our experience in conducting a variety of SMI research for over 25 years offers strong support for successful completion of the proposal.", "keywords": [ "Adopted", "Adoption", "Affect", "Area", "Award", "Bipolar I", "Breathing Exercises", "COVID-19", "Characteristics", "Clinic", "Clinical", "Cognition", "Cognitive deficits", "Communities", "Community Integration", "Complementary Medicine", "Consent", "Consolidated Framework for Implementation Research", "Consult", "Data", "Disease", "Elements", "Employment", "Ensure", "Exercise", "Family", "Frequencies", "Goals", "Health", "Health Personnel", "Healthcare", "Home", "Hybrids", "Impaired cognition", "Impairment", "India", "Individual", "Integrative Medicine", "Intervention", "Interview", "Leisures", "Life", "Life Style", "Measures", "Mental Health", "Mission", "Muscle Contraction", "Outcome", "Participant", "Patient Self-Report", "Patients", "Pattern", "Persons", "Pharmaceutical Preparations", "Physical Fitness", "Pilot Projects", "Population", "Post-Traumatic Stress Disorders", "Posture", "Prevalence", "Protocols documentation", "Publishing", "Quality of life", "Randomized", "Randomized Controlled Trials", "Recording of previous events", "Refractory", "Regulation", "Rehabilitation therapy", "Relaxation", "Research", "Research Design", "Role", "Rural Community", "Safety", "Schedule", "Schizoaffective Disorders", "Schizophrenia", "Services", "Social Functioning", "Socialization", "Strategic Planning", "Stretching", "Substance Use Disorder", "Suicide prevention", "Supervision", "Symptoms", "Techniques", "Testing", "Time", "Training", "Veterans", "Yoga", "alcohol use disorder", "arm", "base", "cognitive benefits", "comorbidity", "comparative efficacy", "cost", "design", "disability", "effectiveness implementation study", "efficacy study", "exercise intervention", "exercise program", "exercise training", "experience", "future implementation", "implementation efforts", "implementation facilitators", "improved", "ineffective therapies", "instructor", "interest", "long-term rehabilitation", "mindfulness", "performance based measurement", "physically handicapped", "primary outcome", "programs", "secondary outcome", "severe mental illness", "skills", "social", "study characteristics", "tool", "treatment arm", "treatment as usual", "uptake", "virtual" ], "approved": true } }, { "type": "Grant", "id": "8006", "attributes": { "award_id": "1I01BX005411-01", "title": "COVID-19: Understanding The Role of Corona Virus InducedDisruption Of Alveolar Type 2 Cell Function And SurfactantHomeostasis In The Pathogenesis Of COVID-19 AcuteRespiratory Distress Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2022-12-31", "award_amount": null, "principal_investigator": { "id": 22384, "first_name": "MICHAEL FRANCIS", "last_name": "BEERS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1488, "ror": "https://ror.org/03j05zz84", "name": "Philadelphia VA Medical Center", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1488, "ror": "https://ror.org/03j05zz84", "name": "Philadelphia VA Medical Center", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "The Severe Acute Respiratory Syndrome (SARS)-associated coronavirus 2 (SCoV2) is the cause of COVID-19 syndrome which is marked by a refractory acute lung injury that results in dramatic hypoxic respiratory failure and high mortality. Despite the recurrent health and economic devastation produced by novel coronaviruses (nCoV) over the past 20 years including SCoV2 as well as its predecessors SCoV1, and MERS-CoV, there remains a significant unmet need both for a clearer understanding of virus-host cell interactions as well as identification of new therapeutic targets. To address these issues with the ultimate goal of improving the health and outcomes of veterans with COVID-19, we have assembled a team of internationally recognized scientists with expertise in coronavirus virology and in lung biology coupled with a strong foundation of our own prior work on surfactant biology, lung injury, and fibrotic repair funded, in part, by the VA Merit Review program. Utilizing this expertise, this proposal is directed at filling in large knowledge gaps that exist in the pathogenesis of nCoV induced respiratory failure. The motivation for this investigation has been fueled by the recent recognition that the alveolar type 2 (AT2) epithelial cell of the distal lung has emerged as an important portal of entry for SCoV- 2. The central hypothesis of this application is that AT2 cells infected with nCoV acquire defects in surfactant biosynthesis/metabolism, activate cellular stress pathways, and develop alterations in progenitor cell function all of which promote hypoxic respiratory failure, persistent lung inflammation and injury, and impact recovery through effects on epithelial repair capacity. To test this, we will leverage an established murine model of CoV infection (MHV-1) with a pulmonary phenotype combined with reductionist studies supported by ex vivo infection of primary human AT2 cells obtained from a robust human lung pipeline with an already in hand SARS-CoV-2 isolate. Our experimental approach will interrogate these preclinical models using tools and reagents available in our program, to map the effect of CoV infection on distal lung cell populations with a focus on identifying and translating molecular mechanisms linking the disrupted AT2 function with altered surfactant biology and proinflammatory/profibrotic cell cross talk in the alveoilar niche. In Specific Aim 1, we will first define temporal changes in distal lung epithelial endophenotypes focusing on the ontogeny of the disruption of AT2 homeostasis by viral infection using a well characterized mouse model of MHV-1 lung infection. Using both unbiased approaches such as transcriptomic profiling as well as classical cell biology and biochemistry this aim will investigate CoV induced changes in surfactant metabolism/biophysical activity, AT2 cell stress (i.e. ER stress, proteasome dysfunction, autophagy malfunction, changes in mitochondrial dynamics/ / bioenergetics) and AT2 progenitor cell function. In Specific Aim 2, armed with this “functional map” of the mouse CoV-lung and aberrant AT2 behaviors, we will translate the identified lead targets and mechanisms to human AT2 cells utilizing both primary AT2 cultures as well as precision cut lung slices (PCLS) infected with SARS-CoV-2. The research design involves the analysis of virus-dependent AT2 surfactant protein and lipid metabolism, interrogation of AT2 cell quality control pathways, and functional evaluation of AT2 progenitor function phenotypes in the SCoV-2 infected human epithelial cells. By understanding the path to epithelial injury / dysfunction from nCoV, the mechanisms and affected lung cell populations identified using these models will improve the understanding of sCOV2/COVID- 19 syndrome, promote identification of new target pathways, and can be cross-purposed to test emerging therapies for both the current and future nCoV pandemics.", "keywords": [ "2019-nCoV", "ACE2", "Acute Lung Injury", "Address", "Adult Respiratory Distress Syndrome", "Affect", "Alveolar", "Anabolism", "Apoptosis", "Autophagocytosis", "Behavior", "Berlin", "Big Data", "Biochemistry", "Bioenergetics", "Biology", "Biophysics", "COVID-19", "COVID-19 pandemic", "COVID-19 pathogenesis", "Caring", "Catalogs", "Cell Communication", "Cell Ontogeny", "Cell model", "Cell physiology", "Cells", "Cellular Stress", "Cellular biology", "Characteristics", "Cicatrix", "Clinical", "Coronavirus", "Coronavirus Infections", "Coupled", "Data", "Defect", "Development", "Disease", "Dissociation", "Distal", "Distress", "Epidemic", "Epithelial", "Epithelial Cells", "Evaluation", "Foundations", "Functional disorder", "Funding", "Future", "Genetic", "Goals", "Gold", "Growth", "Hand", "Health", "Homeostasis", "Human", "Hypoxemia", "Impairment", "In Vitro", "Infection", "Inflammatory", "Innate Immune Response", "International", "Investigation", "Knowledge", "Lead", "Link", "Lung", "Lung Capacity", "Lung Inflammation", "Lung diseases", "Lung infections", "Maintenance", "Maps", "Mediating", "Metabolism", "Middle East Respiratory Syndrome Coronavirus", "Mitochondria", "Modeling", "Molecular", "Molecular Target", "Morbidity - disease rate", "Motivation", "Mus", "Natural Immunity", "Organoids", "Outcome", "Pathogenesis", "Pathway interactions", "Peripheral", "Pharmacology", "Phenotype", "Physiological", "Population", "Positioning Attribute", "Pre-Clinical Model", "Primary Infection", "Program Reviews", "Proteins", "Pulmonary Surfactants", "Quality Control", "Radiology Specialty", "Reagent", "Recovery", "Recurrence", "Refractory", "Reporting", "Research Design", "Residual state", "Respiratory Failure", "Role", "SARS coronavirus", "Scientist", "Severities", "Signal Pathway", "Slice", "Survivors", "Syndrome", "System", "Techniques", "Technology", "Testing", "Therapeutic", "Time", "Translating", "Ubiquitin", "Veterans", "Viral", "Virus", "Virus Diseases", "Work", "alveolar epithelium", "arm", "base", "biological adaptation to stress", "cytokine", "effective therapy", "endophenotype", "endoplasmic reticulum stress", "epithelial injury", "epithelial repair", "experience", "health economics", "immunopathology", "improved", "in vivo", "induced pluripotent stem cell", "lipid metabolism", "lung injury", "lung repair", "mortality", "mouse model", "multicatalytic endopeptidase complex", "new therapeutic target", "novel", "novel coronavirus", "novel s" ], "approved": true } }, { "type": "Grant", "id": "8014", "attributes": { "award_id": "1I01BX005432-01", "title": "COVID-19: Elucidating the Role of the NasalEpithelium in SARS-CoV-2 Infection, Transmission, and Prevention", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2022-12-31", "award_amount": null, "principal_investigator": { "id": 22556, "first_name": "Noam A", "last_name": "Cohen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1488, "ror": "https://ror.org/03j05zz84", "name": "Philadelphia VA Medical Center", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1488, "ror": "https://ror.org/03j05zz84", "name": "Philadelphia VA Medical Center", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe acute respiratory syndrome coronavirus SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19) has led to a pandemic with a mortality of approximately 3.5% and a wide range of morbidity outcomes negatively impacted by pre-existing conditions. Given the prevalence of pre-existing comorbid conditions in Veterans, it is imperative to understand the mechanisms of how SARS-CoV-2 invades and replicates within the barrier defense cells of the nose, which is the primary portal for viral entry. Furthermore, current data suggests that the nasal carriage functions as a potential reservoir for viral persistence and transmission (i.e., shedding) at times that are both prior to and during the manifestation of severe respiratory symptoms. This project utilizes a unique biobank of cryopreserved nasal cells collected from over 1000 individuals over 15 years to understand the critical issues surrounding SARS-CoV-2 interaction with the human nasal epithelia. Paradoxically, while SARS-CoV-2 can be detected in nasal swabs prior to its detection in sputum, there is a paucity of rhinologic symptoms (<5% with nasal congestion) associated with COVID-19, with the exception of reversible anosmia in 30-70% of patients. This is particularly problematic because up to 25% of infected individuals remain asymptomatic, but can continue to spread SARS-CoV-2 through airborne droplets. This work seeks to elucidate both the mechanisms controlling which epithelial cell lineages become infected with virus and the type of immune response generated within infected or neighboring epithelia. Through this approach, we will shed light on the issue of why certain individuals never develop symptoms while others progress to severe respiratory failure and death. We will focus on the SARS-CoV-2 receptor Angiotensin Converting Enzyme 2 (ACE2), which is essential and sufficient for the virus to enter cells. Our preliminary data generated from single cell RNA analysis of primary human sinonasal tissue demonstrates that ACE2 is expressed in discrete clusters of nasal epithelia. ACE2- specific immunostaining of human nasal epithelial cells ex vivo and primary ciliated air liquid interface (ALI) cultures corroborates the sc-RNAseq data. Furthermore, our data show that inoculation of primary ALI cultures with SARS-CoV-2 results in approximately 1%-25% of cells becoming infected, suggesting a selective process. These data indicate that we are uniquely poised to test the hypothesis that ACE2 expressing cells constitute a unique reservoir of viral replication and are likely to mount an inflammatory cytokine response that is distinct from non-infected epithelia. Using our established team of experts in nasal epithelial cell biology, viral pathogenesis, inflammatory cytokine biology and genetics we will determine the following: A) which types of epithelia are virally infected, B) what are the local inflammatory cascades in infected vs. non-infected cells, and C) will pharmacologic manipulation of the epithelial innate defense pathways significantly alter SARS-CoV-2 ability to infect, replicate and be released from human nasal epithelia. Successful completion of this work is likely to have a major impact on development of novel strategies to combat COVID19 disease progression within the general population and especially in the U.S. Veteran population.", "keywords": [ "2019-nCoV", "ACE2", "Address", "Affect", "Age", "Air", "Anosmia", "Apical", "Asthma", "Basal Cell", "Biology", "Bronchitis", "COVID-19", "Caring", "Cell Lineage", "Cells", "Cellular biology", "Cessation of life", "Chronic Obstructive Airway Disease", "Collaborations", "Communities", "Congestive", "Cryopreservation", "Data", "Detection", "Development", "Disease Progression", "Double-Stranded RNA", "Epithelial", "Epithelial Cells", "Functional disorder", "Future", "Gender", "General Population", "Genetic", "Genotype", "Goals", "Goblet Cells", "Growth", "Harvest", "Health", "Healthcare Systems", "Human", "Immune", "Immune response", "Immunologic Receptors", "Individual", "Infection", "Inflammatory", "Inflammatory Response Pathway", "Invaded", "Kinetics", "Knowledge", "Lead", "Light", "Liquid substance", "Lung diseases", "Malignant neoplasm of lung", "Medical", "Morbidity - disease rate", "Mucins", "Mucous Membrane", "Mucous body substance", "Nasal Epithelium", "Natural Immunity", "Nitric Oxide", "Nose", "Nucleocapsid Proteins", "Outcome", "Pathway interactions", "Patients", "Pennsylvania", "Peptide Hydrolases", "Pharmacology", "Predisposition", "Prevalence", "Prevention", "Process", "Production", "Prophylactic treatment", "Protocols documentation", "Pulmonary Emphysema", "RNA analysis", "Race", "Resources", "Respiration Disorders", "Respiratory Failure", "Respiratory Signs and Symptoms", "Rhinitis", "Role", "SARS coronavirus", "SARS-CoV-2 infection", "Sampling", "Sinusitis", "Sputum", "Structure of respiratory epithelium", "Symptoms", "TMPRSS2 gene", "Testing", "Time", "Tissues", "Type 2 Angiotensin II Receptor", "Universities", "Veterans", "Viral", "Viral Genome", "Viral Pathogenesis", "Viral reservoir", "Virus", "Virus Diseases", "Virus Replication", "Virus Shedding", "Vulnerable Populations", "Work", "antimicrobial peptide", "asthma exacerbation", "biobank", "biosafety level 3 facility", "burden of illness", "combat", "comorbidity", "cytokine", "demographics", "discrete time", "experimental study", "high risk", "in vitro Model", "innate immune pathways", "insight", "military veteran", "mortality", "nasal swab", "novel strategies", "pandemic disease", "particle", "prophylactic", "racial disparity", "receptor", "screening", "single-cell RNA sequencing", "success", "targeted treatment", "transcriptome sequencing", "transmission process", "ultraviolet irradiation" ], "approved": true } }, { "type": "Grant", "id": "8016", "attributes": { "award_id": "1I01RX003666-01", "title": "Chronic Lung Disease and COVID-19: Understanding Severity, Recovery and Rehabilitation Needs (LAUREL Study)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2024-12-31", "award_amount": null, "principal_investigator": { "id": 22583, "first_name": "Kristina Anne", "last_name": "Crothers", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1512, "ror": "", "name": "VA PUGET SOUND HEALTHCARE SYSTEM", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22584, "first_name": "Aaron P.", "last_name": "Turner", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1512, "ror": "", "name": "VA PUGET SOUND HEALTHCARE SYSTEM", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 (SARS2) infection, which leads to COVID-19, is a global pandemic. Chronic lung disease (CLD), particularly chronic obstructive pulmonary disease (COPD), has emerged as a risk factor for infection and severity of COVID-19. Currently, very little is known of the long-term consequences of COVID-19 and how factors such as CLD, other comorbidities and social determinants of health (SDOH) influence the trajectory of recovery in survivors. While similar complications for COVID-19 survivors and risk factors for poor health recovery may be expected as in other causes of pneumonia and critical illness, long term outcomes of COVID- 19 have not been characterized or quantified. Patients who are hospitalized and critically ill are anticipated to have greater functional deficits, but even those with mild and moderate COVID-19 may have significant impacts on function given systemic involvement of infection; rehabilitation needs may be more likely to be under-recognized and unmet in many of these patients. Overall, functional outcomes may be worse than expected in all COVID-19 patients because of prolonged length of illness and barriers to receiving rehabilitation services, including restricted face-to-face interactions, limited capacity, and limited access for many. Because CLD is associated with increased frailty and impaired function, patients with CLD may be particularly vulnerable not only to infection but also sequalae of COVID-19. Given the current physical distancing environment, we urgently need a new paradigm for rehabilitation of patients recovering from COVID-19 that can inform and apply to other causes of pneumonia as well. In this proposal we will determine patient rehabilitation needs across the spectrum of severity of COVID-19, assessing if needs differ by CLD, comorbidity burden, SDOH or other patient risk factors. We will also assess the feasibility and acceptability of a novel, virtually-delivered, home-based personalized telerehabilitation program for survivors of COVID-19 that contains a COVID Reactivation and Engagement (CORE) intervention with exercise and dyspnea management and additional personalized modules based on patient needs. We will recruit patients treated for COVID-19 as outpatients or discharged directly home for this program. We have a multidisciplinary team with expertise in rehabilitation medicine, psychology, pulmonary, critical care, nursing, complementary and integrative health, quantitative and qualitative observational research and clinical trials, and will accomplish three separate aims: 1) Determine patient factors associated with severity and complications of COVID-19 utilizing VA EHR data; 2) Determine self-reported functional outcomes and trajectory of recovery after COVID- 19 in a prospective study using mixed methods; and 3) Examine the feasibility and acceptability of a virtually- delivered, home-based rehabilitation intervention for survivors of COVID-19, with components based on an individual patient’s needs. Results will characterize the recovery from COVID-19 and identify rehabilitation and care needs across domains of services that can be offered within VA. Our pilot study will inform larger trials to test the efficacy of this newly-developed program to improve functioning, reduce secondary symptoms, and improve quality of life among individuals recovering from COVID-19.", "keywords": [ "Acute", "Admission activity", "Anxiety", "COVID-19", "COVID-19 patient", "COVID-19 severity", "COVID-19 treatment", "Cardiac", "Cardiovascular system", "Caregivers", "Caring", "Cessation of life", "Chronic", "Chronic Obstructive Airway Disease", "Chronic lung disease", "Classification", "Clinical", "Clinical Trials", "Cognition", "Cognitive", "Complementary Health", "Coronavirus", "Critical Illness", "Data", "Dialysis procedure", "Disease", "Dyspnea", "Dyspnea Management", "Electronic Health Record", "Environment", "Event", "Exercise", "Future", "Health", "Healthcare Systems", "Home", "Hospitalization", "Hospitals", "Impairment", "Individual", "Infection", "Influenza", "Inpatients", "Integrative Medicine", "Intensive Care Units", "International", "Intervention", "Interview", "Location", "Lung", "Mental Depression", "Mental Health", "Methods", "Nurses", "Observational Study", "Outcome", "Outpatients", "Oxygen", "Pain", "Patient Recruitments", "Patient Self-Report", "Patient risk", "Patient-Focused Outcomes", "Patients", "Personal Satisfaction", "Physical Function", "Physical Medicine", "Pilot Projects", "Pneumonia", "Predisposition", "Prospective Studies", "Psychology", "Quality of life", "Recovery", "Rehabilitation therapy", "Reporting", "Risk", "Risk Factors", "SARS-CoV-2 infection", "Services", "Severities", "Stroke", "Surveys", "Survivors", "Symptoms", "Syndrome", "Testing", "Time", "Veterans", "Veterans Health Administration", "acceptability and feasibility", "base", "community acquired pneumonia", "comorbidity", "coronavirus disease", "critical care nursing", "design", "disability", "efficacy testing", "feasibility testing", "follow-up", "frailty", "functional outcomes", "health administration", "health related quality of life", "hospital readmission", "illness length", "improved", "improved functioning", "individual patient", "infection risk", "mortality", "multidisciplinary", "novel", "pandemic disease", "programs", "prospective", "rehabilitation paradigm", "rehabilitation service", "rehabilitative care", "satisfaction", "social health determinants", "telerehabilitation", "uptake", "virtual delivery" ], "approved": true } }, { "type": "Grant", "id": "8031", "attributes": { "award_id": "1I01BX005428-01", "title": "COVID-19: Characterizing trained immune responses to COVID-19", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2022-12-31", "award_amount": null, "principal_investigator": { "id": 23928, "first_name": "JONATHAN P", "last_name": "MOORMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1662, "ror": "", "name": "JAMES H QUILLEN VA MEDICAL CENTER", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1662, "ror": "", "name": "JAMES H QUILLEN VA MEDICAL CENTER", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "In late 2019, a novel human betacoronavirus emerged in Wuhan, China and subsequently led to pandemic spread. Designated Severe Acute Respiratory Virus 2 (SARS CoV-2), this virus has spawned a coronaviral infection (COVID-19) that has threatened world populations and overwhelmed healthcare systems globally. Host immune responses during COVID-19 clearly play a significant role in viral clearance as well as pulmonary progression, but these responses are yet to be characterized. Most notably, the innate immune responses required for viral clearance and resistance to repeated infections are not yet known. Recent studies also suggest that these innate immune responses can also form immunologic memory (“trained immunity”) that occurs independently of B and T cells and results from epigenetic reprogramming of monocytes, macrophage and NK cell functions that alters their intracellular signaling and cellular metabolism patterns. This reprogramming allows them to acquire enhanced capability to respond to secondary stimulation by related or unrelated infectious agents. Because data from related coronaviruses suggest that innate immune responses are fundamentally important to pathogenesis, we hypothesize that NK/monocyte responses to viral proteins are necessary to maximize host immune responses. In this proposal, we will comprehensively investigate the importance of innate immune cells in the development of anamnestic adaptive responses to SARS CoV-2 antigen, and the role of NK and monocytes/macrophages in trained innate immune responses to viral antigen, from a clinically characterized cohort of COVID-19 patients following recovery. In aim 1, we will determine the importance of innate immune responses in responding to repeat exposure to viral antigens following COVID-19 recovery by 1) assessing the necessity of innate immune cells in generating anamnestic adaptive cellular responses to SARS CoV-2, and 2) characterizing the cross-reactivity of betacoronaviral antigens in inducing NK/monocyte responses including phenotypic changes, activation, proliferation, and cytokine expression, in COVID-recovered subjects. In aim 2, we identify innate trained immune responses to SARS CoV-2 antigens following COVID-19 recovery by examining if either NK cells or monocytes/macrophages from COVID-19 recovered subjects exhibit innate immune memory to SARS CoV-2 as assayed by functional, metabolic, and epigenetic changes These novel translational studies will produce key, relevant data on host immunity to COVID-19 infection, informing vaccine design and enhancing our understanding of innate immune memory and the correlates of protective immunity.", "keywords": [ "2019-nCoV", "Acute", "Adaptive Immune System", "Antigens", "B-Lymphocytes", "Biological Assay", "C Type Lectin Receptors", "COVID-19", "COVID-19 pathogenesis", "COVID-19 patient", "Cell physiology", "Cells", "China", "Clinical", "Complex", "Consensus", "Coronavirus", "Data", "Development", "Elderly", "Epigenetic Process", "Exhibits", "Exposure to", "Gene Expression Regulation", "Healthcare Systems", "Human", "Immune", "Immune response", "Immune system", "Immunity", "Immunologic Memory", "Infection", "Infectious Agent", "Innate Immune Response", "Lead", "Link", "Lung", "Lung diseases", "Mediating", "Metabolic", "Metabolism", "Middle East Respiratory Syndrome Coronavirus", "Molecular", "Natural Immunity", "Natural Killer Cells", "Nucleic Acids", "Pathogenesis", "Patients", "Pattern", "Pattern recognition receptor", "Phenotype", "Play", "Population", "Process", "Recovery", "Resistance", "Role", "SARS coronavirus", "SARS-CoV-2 antigen", "SARS-CoV-2 exposure", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Secondary to", "Signal Transduction", "T-Lymphocyte", "Training", "Vaccine Design", "Viral", "Viral Antigens", "Viral Proteins", "Virus", "Virus Diseases", "Vulnerable Populations", "adaptive immune response", "adaptive immunity", "betacoronavirus", "cohort", "coronavirus disease", "cross reactivity", "cytokine", "human coronavirus", "macrophage", "monocyte", "novel", "pandemic disease", "pathogen", "receptor", "respiratory virus", "response", "translational study" ], "approved": true } }, { "type": "Grant", "id": "8032", "attributes": { "award_id": "5I01BX005428-02", "title": "COVID-19: Characterizing trained immune responses to COVID-19", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2022-12-31", "award_amount": null, "principal_investigator": { "id": 23928, "first_name": "JONATHAN P", "last_name": "MOORMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1662, "ror": "", "name": "JAMES H QUILLEN VA MEDICAL CENTER", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1662, "ror": "", "name": "JAMES H QUILLEN VA MEDICAL CENTER", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "In late 2019, a novel human betacoronavirus emerged in Wuhan, China and subsequently led to pandemic spread. Designated Severe Acute Respiratory Virus 2 (SARS CoV-2), this virus has spawned a coronaviral infection (COVID-19) that has threatened world populations and overwhelmed healthcare systems globally. Host immune responses during COVID-19 clearly play a significant role in viral clearance as well as pulmonary progression, but these responses are yet to be characterized. Most notably, the innate immune responses required for viral clearance and resistance to repeated infections are not yet known. Recent studies also suggest that these innate immune responses can also form immunologic memory (“trained immunity”) that occurs independently of B and T cells and results from epigenetic reprogramming of monocytes, macrophage and NK cell functions that alters their intracellular signaling and cellular metabolism patterns. This reprogramming allows them to acquire enhanced capability to respond to secondary stimulation by related or unrelated infectious agents. Because data from related coronaviruses suggest that innate immune responses are fundamentally important to pathogenesis, we hypothesize that NK/monocyte responses to viral proteins are necessary to maximize host immune responses. In this proposal, we will comprehensively investigate the importance of innate immune cells in the development of anamnestic adaptive responses to SARS CoV-2 antigen, and the role of NK and monocytes/macrophages in trained innate immune responses to viral antigen, from a clinically characterized cohort of COVID-19 patients following recovery. In aim 1, we will determine the importance of innate immune responses in responding to repeat exposure to viral antigens following COVID-19 recovery by 1) assessing the necessity of innate immune cells in generating anamnestic adaptive cellular responses to SARS CoV-2, and 2) characterizing the cross-reactivity of betacoronaviral antigens in inducing NK/monocyte responses including phenotypic changes, activation, proliferation, and cytokine expression, in COVID-recovered subjects. In aim 2, we identify innate trained immune responses to SARS CoV-2 antigens following COVID-19 recovery by examining if either NK cells or monocytes/macrophages from COVID-19 recovered subjects exhibit innate immune memory to SARS CoV-2 as assayed by functional, metabolic, and epigenetic changes These novel translational studies will produce key, relevant data on host immunity to COVID-19 infection, informing vaccine design and enhancing our understanding of innate immune memory and the correlates of protective immunity.", "keywords": [ "2019-nCoV", "Acute", "Adaptive Immune System", "Antigens", "B-Lymphocytes", "Biological Assay", "C Type Lectin Receptors", "COVID-19", "COVID-19 pathogenesis", "COVID-19 patient", "Cell physiology", "Cells", "China", "Clinical", "Complex", "Consensus", "Coronavirus", "Data", "Development", "Elderly", "Epigenetic Process", "Exhibits", "Exposure to", "Gene Expression Regulation", "Healthcare Systems", "Human", "Immune", "Immune response", "Immune system", "Immunity", "Immunologic Memory", "Infection", "Infectious Agent", "Innate Immune Response", "Lead", "Link", "Lung", "Lung diseases", "Mediating", "Metabolic", "Metabolism", "Middle East Respiratory Syndrome Coronavirus", "Molecular", "Natural Immunity", "Natural Killer Cells", "Nucleic Acids", "Pathogenesis", "Patients", "Pattern", "Pattern recognition receptor", "Phenotype", "Play", "Population", "Process", "Recovery", "Resistance", "Role", "SARS coronavirus", "SARS-CoV-2 antigen", "SARS-CoV-2 exposure", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Secondary to", "Signal Transduction", "T-Lymphocyte", "Training", "Vaccine Design", "Viral", "Viral Antigens", "Viral Proteins", "Virus", "Virus Diseases", "Vulnerable Populations", "adaptive immune response", "adaptive immunity", "betacoronavirus", "cohort", "coronavirus disease", "cross reactivity", "cytokine", "human coronavirus", "macrophage", "monocyte", "novel", "pandemic disease", "pathogen", "receptor", "respiratory virus", "response", "translational study" ], "approved": true } }, { "type": "Grant", "id": "8065", "attributes": { "award_id": "1I01BX005413-01", "title": "Lung Innate COVID-19 Defense Specific to Veterans Risk Characteristics", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2022-12-31", "award_amount": null, "principal_investigator": { "id": 23960, "first_name": "Kristina L", "last_name": "Bailey", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1645, "ror": "", "name": "OMAHA VA MEDICAL CENTER", "address": "", "city": "", "state": "NE", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23807, "first_name": "Todd A", "last_name": "Wyatt", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1645, "ror": "", "name": "OMAHA VA MEDICAL CENTER", "address": "", "city": "", "state": "NE", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 1645, "ror": "", "name": "OMAHA VA MEDICAL CENTER", "address": "", "city": "", "state": "NE", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 is now a global pandemic requiring a rapid and concerted response from the scientific and medical community. Based upon recent epidemiology derived only months earlier from the earliest affected countries, the pathogenesis of the SARS-CoV-2 virus and clinical outcomes from COVID-19 are far worse in individuals with certain pre-existing conditions and those of advanced age. It is essential to the health of Veterans to fully define which at-risk conditions particularly impact them and their unique needs and to do so immediately in order to empower clinical preventive care during this and future viral pandemics. Compared to the general public, the Veterans population can be characterized by older age, cigarette smoking leading to pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD), and alcohol use disorders (AUD). Our knowledge about how such characteristics impact SARS-CoV-2 pathogenesis is limited. However, results from our previous VA-supported research have already demonstrated that old age and AUD are associated with cilia dysfunction. Our results also demonstrate that AUD results in decreased surfactant anti-microbial action. Surfactant protein D has been documented to specifically bind to and neutralize the Spike protein of coronavirus. We hypothesize that altered innate lung defense at the level of mucociliary clearance, anti- microbial surfactants, and viral receptor function will negatively impact susceptibility and pathogenesis of SARS-CoV-2, placing Veterans particularly in harm’s way. Our assembled team of investigators include a VA Research Career Scientist with 25 years’ experience in the impact of alcohol on lung injury and repair, a physician-scientist at the VA whose expertise is on the impact of age in lung function, and a microbiologist who is already experienced in working with SARS-CoV-2 under BSL3 conditions. Combined with our existing biobank of human lung cells and tissues, we propose to address our hypothesis by identifying any differences in SARS-CoV-2 infection responses between normal airway epithelium and lung macrophages and those cells collected from individuals with COPD, with AUD, or of old age. We will specifically identify in these groups any changes in cilia beat controlling clearance, surfactant protein D expression/structure/function, and known SARS-CoV-2 receptors. Such studies will be performed for the first time in these high-risk groups common to the VA population. Defining the modalities of risk will empower clinicians to make informed clinical preventive care decisions for Veterans.", "keywords": [ "2019-nCoV", "ACE2", "Address", "Affect", "Age", "Aging", "Alcohol abuse", "Alcohols", "Alveolar Macrophages", "Binding", "COVID-19", "COVID-19 mortality", "COVID-19 pandemic", "Cells", "Cessation of life", "Characteristics", "Chronic Obstructive Airway Disease", "Chronic lung disease", "Cilia", "Clinical", "Collectins", "Communities", "Contracts", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Country", "Data", "Defense Mechanisms", "Defensins", "Disease", "Elderly", "Enzymes", "Epidemiology", "Epithelial Cells", "Functional disorder", "Future", "GRP78 gene", "General Population", "Health", "Human", "Immune", "Impairment", "Individual", "Infection", "Innate Immune System", "Knowledge", "Lead", "Lung", "Lung diseases", "Medical", "Modality", "Mucociliary Clearance", "Mucous body substance", "Natural Immunity", "Outcome", "Patients", "Physicians", "Population", "Predisposing Factor", "Predisposition", "Preventive care", "Process", "Proteins", "Pulmonary Surfactant-Associated Protein D", "Research", "Research Personnel", "Research Support", "Risk", "Risk Factors", "Role", "Route", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Scientist", "Site", "Smoking", "Structure", "Symptoms", "Testing", "Time", "Tissues", "Veterans", "Viral", "Virus", "Virus Diseases", "Virus Receptors", "Vulnerable Populations", "Work", "Writing", "age effect", "airway epithelium", "alcohol misuse", "alcohol use disorder", "antimicrobial", "base", "biobank", "career", "cigarette smoking", "experience", "high risk", "high risk population", "human old age (65+)", "infection rate", "injury and repair", "lung injury", "macrophage", "military veteran", "mortality", "novel coronavirus", "pandemic disease", "particle", "prevent", "pulmonary function", "receptor", "receptor function", "response", "skills", "surfactant" ], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1397, "count": 13961 } } }