Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=-program_reference_codes
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_reference_codes", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=-program_reference_codes", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=-program_reference_codes", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=-program_reference_codes" }, "data": [ { "type": "Grant", "id": "11701", "attributes": { "award_id": "1T32HL166128-01A1", "title": "Training in Translational Science and Cardiovascular Research", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 26494, "first_name": "SEUNG KYOON KYOON", "last_name": "Woo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2028-06-30", "award_amount": 529763, "principal_investigator": { "id": 27569, "first_name": "Nabil J", "last_name": "Alkayed", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "This proposal seeks support for a well-established training program in translational cardiovascular research for MD and PhD postdoctoral fellows at Oregon Health & Science University (OHSU). The training program has a long history of training excellence and is an essential component of the educational and training activities of The Knight Cardiovascular Institute. Over the past decade, the program has trained many fellows, who have been successful in obtaining independent positions in academics. Our trainees included equal numbers of men and women and MDs and PhDs, and included fellows from under-represented minority groups. We request funding for 6 post-doctoral fellows per year (3 positions for two years each). The program offers exciting opportunities for bench to bedside, multidisciplinary training in one of three established Training Hubs that specialize in: 1) Cardiovascular Regulation, which includes physiological regulation, ischemia-reperfusion and hypertension, 2) Cardiovascular Inflammation, which includes atherosclerosis, diabetes, thrombosis, and viral infections with relevance to cardiovascular disease (including COVID-19), and 3) Cardiovascular Development, which includes cardiovascular genetics, genomics and fetal programming. The faculty mentors are highly recognized and funded scientists who have a strong track record of training postdoctoral fellows. The program is highly interdisciplinary and mentors' expertise cover a wide range of the translational spectrum. Laboratory research is supplemented by course work, seminars, journal club, and meetings within a specific science group. Course work includes research design, biostatistics, cardiovascular physiology and genetics. All trainees participate in responsible conduct of research training, scientific writing, entrepreneurship and team science and leadership training. This program is unique at OHSU in that mentoring is carried out by a multidisciplinary team, and because training is specifically designed to translate basic cardiovascular research into clinical benefit. The primary mentor will be assisted by at least two co-mentors, who complement the primary mentor's expertise by bringing clinical, basic science or technical expertise. The training outcome will be scientists with a broad outlook and a focus on bringing science to the bedside. The application includes a strong recruitment plan for underserved minority trainees and an evaluation process. A Program Advisory Committee monitors the progress of every trainee as they meet specific mileposts in preparation for a research career. In summary, the proposed cardiovascular research training program will provide a unique opportunity for multidisciplinary training, and successful trainees will be well equipped to initiate independent research careers in translational cardiovascular research.", "keywords": [ "Cardiovascular system", "Research", "Training", "Translational Research" ], "approved": true } }, { "type": "Grant", "id": "11702", "attributes": { "award_id": "1U18FD008005-01", "title": "Multi-lab validation of a real-time PCR assay for detection and surveillance of SARS-CoV-2 for companion animal applications.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [ { "id": 26272, "first_name": "Megan", "last_name": "Miller", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2025-06-30", "award_amount": 96119, "principal_investigator": { "id": 24457, "first_name": "Jianfa", "last_name": "Bai", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 197, "ror": "https://ror.org/05p1j8758", "name": "Kansas State University", "address": "", "city": "", "state": "KS", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 27570, "first_name": "Lance W.", "last_name": "Noll", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 197, "ror": "https://ror.org/05p1j8758", "name": "Kansas State University", "address": "", "city": "", "state": "KS", "zip": "", "country": "United States", "approved": true }, "abstract": "Following its emergence in 2019, SARS-CoV-2 spread globally, leading to over 757 million confirmed cases of COVID-19 and over 6.8 million deaths worldwide (WHO COVID19 dashboard, as of Feb 27, 2023). Variants of concern (VOC) have emerged throughout the pandemic (CDC, 2021a). Among the recent of these are Delta, which has been associated with increased pathogenicity, and Omicron and its currently circulating subtypes, which are associated with increased transmissibility (CDC, 2021a). Although humans have served as the primary SARS-CoV-2 reservoir, natural infections have also been reported in animals (Singla et al., 2020), mostly either companion animals, including cats and dogs, or other animals under human care, including tigers, lions, gorillas, snow leopards, otters and spotted hyenas (USDA-APHIS). From August 2021 to present, all confirmed cases of SARS-CoV-2 in companion and exotics species in the U.S have been associated with either Delta or Omicron, which also continue to represent a majority of overall infections in these animal populations since the beginning of the pandemic (USDA-APHIS). Accurate detection and differentiation of major VOCs is important for surveillance of SARS-CoV-2 in these animal populations, and can serve as a useful tool for retrospective studies that may help determine the roles these species played during the pandemic. We have previously developed a multiplex real-time PCR (qPCR) assay for the detection of SARS- CoV-2 and differentiation of Delta and Omicron variants (Tsui et al., 2022). Our objective is to perform a multi- lab validation of the current assay, or an updated assay, and to make the assay publicly available for surveillance and diagnostic research of SARS-CoV-2 in current and pandemic-era animal submissions, respectively. Specific proposal objectives are as follows: 1. In silico re-analysis of SARS-CoV-2 genome sequences to ensure the assay is detecting the currently circulating Omicron sub-variants while still maintaining detection and differentiation of Delta variant. 2. Develop a sample panel for multi-lab validation by creating a SARS-CoV-2-negative canine nasal swab pool matrix that will be spiked, at different concentrations, with SARS-CoV-2 positive animal samples. Synthesized target RNA will be used only if positive animal samples are not available. Absolute concentration of each dilution will be measured by digital PCR, and compared to qPCR testing. 3. Distribute the validation sample panel to collaborating laboratories for multi-lab validations. Testing materials for the panel will include RNA extraction reagents, primers, probes, qPCR reaction reagents and positive controls. 4. Real-time PCR data from each collaborative laboratory will be collected, analyzed for inter-lab performance, then summarized for conference presentation and drafted into a manuscript for publication.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "11703", "attributes": { "award_id": "1R21EB034579-01", "title": "Paper-based high shear hemostatic analytical device", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 6433, "first_name": "Tiffani Bailey", "last_name": "Lash", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2025-04-30", "award_amount": 203241, "principal_investigator": { "id": 27571, "first_name": "David", "last_name": "Bark", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "There are many diseases (e.g. arrhythmias, coronary artery disease, and infections) and situations (e.g. medical devices, trauma, and surgery) that require rapid and accurate point-of-care hemostatic tests, especially when regulating antithrombotics or after a blood transfusion. However, there are few options in resource-limited environments like low- and middle-income countries (LMICs), rural clinics, combat environments, and many others. This is because current hemostatic assays require electrical power, capital expense, skilled technicians, large equipment, and can be slow. As cardiovascular disease increases in LMICs, there is an urgent need to provide innovative tools for these lower resource environments. As an alternative, microfluidic-paper based analytical devices (PAD)s have been developed for low resource settings as a point-of-care technology since these are rapid, cost-effective, portable, disposable, eas-to-use, and typically require electricity. Such devices include the rapid antigen tests developed for COVID-19, which provide critical rapid feedback for making educated health decisions. These can be used almost anywhere with relatively little skill. Our goal is to develop a similar point-of-care tool that we call the Paper-based Clotting Analysis Test (P-CAT). Current PADs are limited for hemostatic analysis since they typically produce low flow conditions that can’t test many of the processes/pathways in primary hemostasis. We have developed a fast-flow PAD that will be incorporated into the P-CAT, enabling us to investigate the spectrum of pathways involved in hemostasis with only a drop (microliters) of blood. P-CATs can be created rapidly and at very little cost, thereby producing high throughput data. Here, we will develop the P-CAT to test blood samples with high specificity and and sensitivity to 1) pathways in primary (platelet-dependent) hemostasis, and 2) intrinsic and extrinsic coagulation cascades in secondary hemostasis. If successful, we will expand upon the P-CAT to incorporate additional biomarkers in an automated point-of-care device that could have a major impact on enabling portable, rapid, and inexpensive tests for hemostasis that can be widely distributed.", "keywords": [ "Anticoagulants", "Arrhythmia", "Biological Assay", "Biological Markers", "Blood", "Blood Glucose", "Blood Platelets", "Blood Tests", "Blood Transfusion", "Blood coagulation", "Blood flow", "Blood specimen", "COVID-19", "Capital", "Cardiovascular Diseases", "Cause of Death", "Characteristics", "Clinic", "Coagulation Process", "Collagen", "Consumption", "Coronary Arteriosclerosis", "Data", "Defect", "Dependence", "Devices", "Diagnostic Equipment", "Disease", "Drops", "Drug Costs", "Electricity", "Environment", "Equipment", "Extracorporeal Membrane Oxygenation", "Feedback", "Fibrinolytic Agents", "Generations", "Goals", "Growth", "Health", "Health Care Costs", "Hemorrhage", "Hemostatic Agents", "Hemostatic function", "Hospitals", "Infection", "Injury", "Ischemia", "Life", "Medical Device", "Microfluidics", "Modeling", "Monitor", "Nature", "Operative Surgical Procedures", "Outcome", "Paper", "Pathway interactions", "Patients", "Persons", "Pharmaceutical Preparations", "Point of Care Technology", "Porosity", "Process", "Resource-limited setting", "Resources", "Rural", "Sampling", "Secondary to", "Sensitivity and Specificity", "Severities", "Speed", "Stenosis", "Technology", "Testing", "Thromboplastin", "Thrombosis", "Thrombus", "Time", "Tissues", "Transfusion", "Trauma", "Warfarin", "Work", "antigen test", "blood product", "clinically relevant", "combat", "cost", "cost effective", "experimental study", "health disparity", "improved", "inhibitor", "innovation", "light weight", "low and middle-income countries", "operation", "point of care", "point-of-care diagnostics", "portability", "prevent", "response", "rural area", "skills", "test strip", "thrombotic", "tool", "user-friendly" ], "approved": true } }, { "type": "Grant", "id": "11704", "attributes": { "award_id": "3K23AA025707-05S1", "title": "Funded extension request for \"Expanding recovery support for emerging adults with alcohol use disorder: Training in the science of social network sites\"", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 27572, "first_name": "BRETT THOMAS", "last_name": "HAGMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2024-04-30", "award_amount": 107999, "principal_investigator": { "id": 27573, "first_name": "Brandon G.", "last_name": "Bergman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: Principal Investigator (PI), Dr. Brandon Bergman, is seeking a 6th year of salary support at $142,560 for his K23 to obtain training and conduct mentored research on recovery-related social network sites and other digital recovery supports. This request includes $100,000 for salary, $32,000 for 32% fringe, and $10,650 for 8% indirect costs. During COVID-19, the outpatient treatment program from which Dr. Bergman’s K23 study initially intended to recruit participants transitioned to, and has continued to operate within, a telehealth-only model. This COVID-related challenge led to insurmountable study recruitment barriers. Under the guidance of primary mentor John Kelly, Dr. Bergman adapted K23 aims that both a) maintain the K23’s scope at the nexus of recovery support services and social technology, and b) allow for all study procedures to be conducted remotely. These studies have been outlined in prior K23 research performance progress reports (RPPR). In brief, study 1 will examine the utility and phenomenology of participation in existing, online recovery support meetings (e.g., Alcoholics Anonymous via Zoom) in adults with moderate/severe alcohol use disorder (N = 60). To promote online recovery support meeting attendance that can be examined scientifically, we developed a clinical linkage and facilitation that will provide personalized recommendations across three online meeting types: 12-step, SMART, and All Recovery (an inclusive and eclectic mutual-help model). Study 2 examines naturalistic, longitudinal effects of online recovery community participation among individuals \"in, seeking, or curious about recovery\" who currently use one of two communities – Intherooms.com or Recovery-related Reddit forums (N = 500). These studies have both been submitted to our Institutional Review Board (IRB) and are ready to launch pending approval. A 6th year of salary support for Dr. Bergman would enable him to continue dedicating 75% effort to these studies. Of note, research funding as initially proposed can be repurposed to carry out Studies 1 and 2. Thus, the PI's salary support is the only additional funding request being proposed in this supplement. This administrative supplement is responsive to NOT-OD-21-052 as the request extends beyond merely addressing productivity issues. The supplement would help to redress barriers to K23 recruitment introduced by the COVID-19 pandemic. In parallel, the additional year of salary support would help to maintain the trajectory of Dr. Bergman's career development and productivity. Consistent with PA-20-272, the proposed supplement will redress COVID-19-related barriers to preserve the near-term and downstream impacts of Dr. Bergman's work on the K23. The supplement will also preserve the likelihood that Dr. Bergman builds a research program responsive to NIAAA and other NIH priorities. For example, a 6th year of salary support will also provide the PI with protected time to prepare and submit an R01 application that builds on and leverages data from these K23 studies to develop and experimentally test a digital recovery support service linkage intervention.", "keywords": [ "Abstinence", "Address", "Administrative Supplement", "Adult", "Alcoholics Anonymous", "Ambulatory Care", "Award", "Behavioral Mechanisms", "COVID-19", "COVID-19 pandemic", "Clinical", "Communities", "Community Participation", "Curiosities", "Data", "Data Analyses", "Data Collection", "Dedications", "Drug Use Disorder", "Drug usage", "Emergency Situation", "Environment", "Facilities and Administrative Costs", "Funding", "Guidelines", "Individual", "Institution", "Institutional Review Boards", "Intervention", "Mainstreaming", "Manuscripts", "Mentors", "Modeling", "National Institute on Alcohol Abuse and Alcoholism", "Outcome", "Participant", "Patient Recruitments", "Performance", "Persons", "Policy Maker", "Preparation", "Principal Investigator", "Procedures", "Productivity", "Progress Reports", "Publications", "Publishing", "Questionnaires", "Recommendation", "Recovery", "Recovery Support", "Report (document)", "Research", "Research Personnel", "Research Support", "Risk", "Science", "Scientist", "Site", "Social Distance", "Social Network", "Social Sciences", "Specific qualifier value", "Technology", "Telemedicine", "Testing", "Time", "Training", "United States National Institutes of Health", "Wages", "Work", "alcohol and other drug", "alcohol use disorder", "behavior change", "career", "career development", "coronavirus disease", "digital", "drinking", "emerging adult", "experience", "meetings", "novel", "outpatient programs", "pandemic disease", "peer", "person centered", "phenomenological models", "preservation", "programs", "prospective", "recovery services", "recruit", "research study", "social", "symposium", "telehealth", "treatment program" ], "approved": true } }, { "type": "Grant", "id": "11705", "attributes": { "award_id": "1R01AI169022-01A1", "title": "Transmission of CoV-2 and the Impact of Spike Protein Evolution", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 26420, "first_name": "MARY KATHERINE", "last_name": "Bradford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2027-06-30", "award_amount": 581630, "principal_investigator": { "id": 27574, "first_name": "Adrianus CM", "last_name": "Boon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 has led to unprecedented disruptions to society, killing more than 6 million people worldwide. It is a respiratory virus whose main mode of transmission is via respiratory droplets and aerosols. Social distancing and vaccines have greatly decreased the rate of infection and transmission. Despite these efforts, SARS-CoV- 2 transmission has continued. Moreover, different variants of concern, harboring signature mutations in the virus attachment Spike protein, have emerged. How these changes affect transmission of SARS-CoV-2 in naïve, infected and immunized individuals is not known. The transmission bottleneck is defined as the number of unique virus particles that establish an infection in the recipient host. This number is important as it determines the rate of evolution of the virus and the immune threshold required for protection from infection. This application will use barcoded or tagged SARS-CoV-2 to quantify how many virus particles establish an infection in the recipient host. We will use the Syrian hamster SARS-CoV-2 airborne transmission model to define how the innate and adaptive immune response in the donor and recipient host effect the number of unique transmission events. Using genetically modified hamsters that are deficient in their type I or III interferon response will be used to measure the role of innate immunity on SARS-CoV-2 transmission to the upper respiratory tract (URT) and subsequent dissemination of the virus to lower respiratory tract (LRT). Transmission and dissemination of SARS-CoV-2 will also be quantified in recipient animals that were previously infected with SARS-CoV-2, immunized with mucosal and systemic COVID-19 vaccines, or received neutralizing IgG and IgA antibodies. Finally, this application will measure the impact of immune escape on the transmission bottleneck in immune recipients. Fundamental insights into respiratory virus transmission and dissemination, transmission bottleneck and defining correlates of protection in the URT and LRT will inform future vaccine efforts against respiratory viruses.", "keywords": [ "2019-nCoV", "ACE2", "Adenovirus Vector", "Aerosols", "Affect", "Agonist", "Animal Model", "Animals", "Antibodies", "Bar Codes", "Binding", "COVID-19 susceptibility", "COVID-19 vaccine", "Cessation of life", "Data", "Dose", "Epitopes", "Event", "Evolution", "Future", "Goals", "Hamsters", "Hour", "Human", "Immune", "Immune response", "Immunity", "Immunization", "Immunize", "Immunoglobulin A", "Immunoglobulin G", "Incubated", "Individual", "Infection", "Innate Immune Response", "Innate Immune System", "Interferons", "Intramuscular", "Kinetics", "Location", "Lower respiratory tract structure", "Measures", "Mesocricetus auratus", "Modeling", "Monoclonal Antibodies", "Mucosal Immunity", "Mucous Membrane", "Mutation", "Natural Immunity", "Pan Genus", "Persons", "Process", "Proteins", "Publishing", "Recombinant Interferon", "Recombinants", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 transmission", "SARS-CoV-2 variant", "Severity of illness", "Social Distance", "Societies", "Testing", "Time", "Upper Respiratory Infections", "Upper respiratory tract", "Vaccinated", "Vaccines", "Variant", "Viral", "Virion", "Virus", "Virus Diseases", "adaptive immune response", "adaptive immunity", "emerging pathogen", "in vivo", "infection rate", "influenzavirus", "insight", "neutralizing monoclonal antibodies", "particle", "pathogenic virus", "prevent", "protective effect", "receptor binding", "respiratory", "respiratory virus", "response", "transmission process", "vaccine delivery", "variants of concern", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "11706", "attributes": { "award_id": "1R44AI177179-01", "title": "Multidimensional antibody engineering to enhance the potency and breadth of a betacoronavirus medical countermeasure", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6908, "first_name": "JENNIFER L.", "last_name": "Gordon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2024-06-30", "award_amount": 283552, "principal_investigator": { "id": 27575, "first_name": "Zachary A", "last_name": "Bornholdt", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2038, "ror": "", "name": "EITR BIOLOGICS, INC.", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The magnitude and duration of the ongoing COVID-19 pandemic have underscored the need to have a well-equipped—and ideally prepositioned—arsenal of antiviral weapons to mount an adequate public health response. A key lesson is that multiple medical countermeasures (MCMs) are needed to maintain potency and efficacy in the face of a rapidly evolving virus. Several approved SARS-CoV-2 vaccines have been paramount to gaining control over the pandemic, reducing both the number of infections and severity of disease for much of the global population. Unfortunately, these vaccines provide little to no protection to immunocompromised individuals who are unable to mount an effective immune response. Half-life extended monoclonal antibodies (mAbs) offer an attractive alternative, as their long half-life and high potency offer instantaneous immunity and vaccine-like protection without requiring the generation of a robust immune response. While >10,000 mAbs and multiple mAb cocktails have been explored over the course of the pandemic and several advanced as therapeutic candidates, they have largely failed to maintain potent activity in the face of prevalent antigenic drift within the SARS-CoV-2 spike protein. Moreover, currently approved vaccines and immunotherapeutics offer no protection from a related b-CoV, Middle East respiratory syndrome (MERS) virus. While small molecule inhibitors such as Paxlovid have shown broad in vitro activity against SARS and MERS, significant issues with COVID-19 rebound following treatment suggest it may not remain efficacious against the more lethal MERS virus. A recently identified antibody, 1249A8 (renamed AR-703), that recognizes a unique and highly conserved epitope in the S2 domain of the coronavirus spike protein offers a potential solution, being refractory to antigenic drift and having broad activity b- CoV activity, inclusive of SARS and MERS. The goal of the proposal is to maximize the clinical utility of AR-703 through multidimensional structure-based approach to increase neutralization potency and expand breadth of AR-703. In parallel, bispecific antibody engineering utilizing a novel bovine ultra-long CDR3 (UL-CDR3) based bispecific platform technology will be explored to introduce synergistic neutralization and resist viral escape. The structures of bovine UL-CDR3s have a demonstrated ability to independently target cryptic highly conserved epitopes, vital to maintaining efficacy to novel viral variants. Combining AR-703 and pan-b-CoV UL-CDR3 into a single bispecific would enable dual engagement of highly conserved neutralizing epitopes offering a potent solution to SARS2 antigenic drift for the immunocompromised while also guarding against related lethal b-CoVs should they emerge in the future.", "keywords": [ "2019-nCoV", "Acceleration", "Address", "Affinity", "Antibodies", "Antibody Binding Sites", "Antigens", "B-Lymphocytes", "Binding", "Biological Assay", "Biological Products", "Bispecific Antibodies", "COVID-19", "COVID-19 pandemic", "COVID-19 vaccine", "Cattle", "Cell Line", "Chinese Hamster Ovary Cell", "Clinical", "Coronavirus spike protein", "Custom", "Dimensions", "Dose", "Drug Kinetics", "Elderly", "Epitopes", "Evaluation", "Formulation", "Future", "Generations", "Genetic Polymorphism", "Glycoproteins", "Goals", "Half-Life", "Hamsters", "Hour", "Immune response", "Immunity", "Immunize", "Immunocompromised Host", "Immunoglobulin G", "Immunotherapeutic agent", "Individual", "Infection", "Lead", "Middle East Respiratory Syndrome", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Modification", "Monoclonal Antibodies", "Mutagenesis", "Mutation", "Names", "Paxlovid", "Peripheral Blood Mononuclear Cell", "Phase", "Population", "Positioning Attribute", "Predisposition", "Production", "Proteins", "Public Health", "Rattus", "Refractory", "Resolution", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Sampling", "Serum", "Severe Acute Respiratory Syndrome", "Severity of illness", "Structure", "Technology", "Testing", "Therapeutic", "Therapeutic Monoclonal Antibodies", "Tissues", "Toxic effect", "Transgenic Mice", "Vaccines", "Variant", "Viral", "Virus", "antibody engineering", "betacoronavirus", "cross reactivity", "group competition", "high risk population", "in vitro activity", "in vivo", "in vivo evaluation", "lead candidate", "medical countermeasure", "nanomolar", "nanotherapeutic", "novel", "pandemic disease", "preclinical development", "prophylactic", "response", "screening", "small molecule inhibitor", "stem", "therapeutic candidate", "vaccine failure", "variants of concern", "weapons" ], "approved": true } }, { "type": "Grant", "id": "11707", "attributes": { "award_id": "1I01CX002400-01A2", "title": "Consequences of social isolation during the COVID-19 pandemic in older adults with and without Alzheimer's disease", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-07-01", "end_date": "2027-06-30", "award_amount": null, "principal_investigator": { "id": 27576, "first_name": "Andrew", "last_name": "Budson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1521, "ror": "", "name": "VA BOSTON HEALTH CARE SYSTEM", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has caused over half a million deaths in the United States alone. Even for those individuals whose physical health and financial security have not been impacted, the consequences of pandemic-induced isolation on mental and cognitive health may be far-reaching— especially for our Veterans. Prior to the pandemic, approximately 10% of older Veterans reported feeling lonely often and 40% indicated feeling lonely some of the time. Due to social distancing guidelines and other measures that limit social contact, loneliness during the pandemic has likely been far greater than these estimates. Decades of research have supported the protective effect of social relationships on cognition in older adulthood; thus, the disruption of social support related to the pandemic may impact cognitive function in the older Veteran population. To address this possibility, we propose a prospective study to examine the relationships between isolation in the pandemic and subsequent cognitive function in healthy older adult Veterans and in older Veterans with Alzheimer’s disease (AD) (Aim 1). In addition, forced isolation is likely not the only factor with important consequences in the pandemic. We propose investigating two other pandemic-related contexts that may either mitigate the effects of isolation in the pandemic or exacerbate the consequences of cognitive impairment on health-related outcomes for older Veterans. First, older Veterans may be able to cope with isolation through use of features of the built environment, such as porches, window views, and public neighborhood space. However, the extent the built environment may be able to mitigate pandemic-related loneliness in older adults is unknown. In Aim 2, we test the hypothesis that built environment factors will mitigate or contribute to social isolation in older Veterans with and without AD. In addition, individuals’ cognition may be impacted by their belief in misconceptions related to social isolation itself. In Aim 3, we test the relationship between cognitive function and the ability to correct misconceptions related to social isolation and AD—and whether such corrections engender changes in behavior. To accomplish Aims 1-3, we will apply questionnaires and neuropsychological tests administered during the first wave of the pandemic (June 2020-June 2021) to 196 participants over three additional one-year time intervals from October 2022 to September 2025. In Aim 1, we will test the relationship between social isolation in the pandemic and cognitive function one, two, and three years later. In Aim 2, we will test whether older Veterans with fewer built environment resources will demonstrate a worsening of social isolation, loneliness, depression, anxiety, and cognition over time. In Aim 3, two objectives will be tested. First, we will determine the extent that individuals with and without cognitive impairment due to AD can successfully change their belief in misconceptions related to social isolation and AD through a correction procedure over time. Second, we will test whether corrections related to changes in behavior at delayed intervals of 1 and 2 years. Preliminary cross-sectional data from our already recruited final sample of older adults (N=196) with and without AD support the relationships between social isolation and cognitive impairment (Aim 1), the built environment and social isolation (Aim 2), and cognitive impairment and misconception correction (Aim 3). As the ramifications of the pandemic continue to unfold for years—possibly decades—it is imperative that we understand the relationship between social isolation and future cognitive impairment in Veterans with and without Alzheimer’s disease.", "keywords": [ "Address", "Adult", "Affect", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease risk", "Anxiety", "Behavior", "Belief", "COVID-19 pandemic", "COVID-19 pandemic effects", "Cessation of life", "Cognition", "Cognitive", "Cognitive Science", "Complex", "Data", "Dementia", "Elderly", "Environment", "Feeling", "Future", "Goals", "Grant", "Guidelines", "Health", "Hippocampus (Brain)", "Home", "Impaired cognition", "Individual", "Light", "Loneliness", "Measures", "Memory Loss", "Mental Depression", "Misinformation", "Modernization", "Moods", "Neighborhoods", "Neuropsychological Tests", "Outcome", "Participant", "Personality", "Personality Character", "Persons", "Procedures", "Prospective Studies", "Psyche structure", "Questionnaires", "Recommendation", "Reporting", "Research", "Resources", "Sampling", "Security", "Shapes", "Social Behavior", "Social Distance", "Social isolation", "Social support", "Stereotyping", "Surveys", "Techniques", "Testing", "Time", "United States", "Variant", "Veterans", "behavior change", "built environment", "cognitive function", "cognitive testing", "coping", "coronavirus disease", "dementia risk", "design", "effective intervention", "emotional factor", "experience", "follow-up", "human old age (65+)", "improved", "long term consequences of COVID-19", "mild cognitive impairment", "military veteran", "neuroinflammation", "pandemic disease", "pandemic response", "physical conditioning", "protective effect", "psychosocial", "recruit", "social cognition", "social contact", "social factors", "social relationships", "time interval", "video chat" ], "approved": true } }, { "type": "Grant", "id": "11708", "attributes": { "award_id": "1R01NS129836-01A1", "title": "Mechanisms and Functions of Cortical Activity to Restore Behavior", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 27577, "first_name": "DAOFEN", "last_name": "CHEN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2028-06-30", "award_amount": 611265, "principal_investigator": { "id": 27578, "first_name": "Diany Paola", "last_name": "Calderon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 825, "ror": "", "name": "WEILL MEDICAL COLL OF CORNELL UNIV", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Monitoring the transition to wakefulness is critical during restoration to consciousness after brain injury, anesthesia, and in those COVID-19 survivors that have altered consciousness. However, we have an imprecise understanding of neural dynamics linked to behavioral changes as subjects awaken. Our previous work discovered that stimulating the anterior nucleus gigantocellularis (aNGC) promotes arousal from a coma-like state. We proposed recruiting multiple arousal pathways through aNGC as an avenue to triggering widespread activation resulting in wakefulness. Notably, aNGC activation increased frontal-motor cortical activity and restored full mobility through modulation of an aNGC-to-frontal-motor-cortex pathway despite high anesthetic concentration exposure. We also showed that animals emerging from diverse coma-like states share a common dynamic process of cortical and motor arousal that can be consistently sequenced from deep to high arousal levels. We identified five cortical periods that tracked restored motor behavior in a hypoglycemic coma and a range of anesthetics, whether inhaled or injected, alongside conventional righting reflex assays. Based on these findings, we postulate that restoring waking is a common progressive process in which cortical patterns contain metrics of consciousness that distinguish reflexive from purposeful movements. We hypothesize that cortical measurements that link neural responsiveness to defined behaviors are an applicable method that can extend the analysis of the recovery of consciousness beyond monitoring reflexive movements. Our proposal deepens our understanding of the contribution of cortical neural subtypes, the neuronal pathways underlying aNGC-induced changes in frontal-motor cortical activity, and the temporal dynamics that distinguish reflexive from the initiation of voluntary behaviors in our rodent-low arousal models. In addition, we will establish the cortical patterns that unpack these behavioral transitions. Since pathological states of unconsciousness are vastly heterogeneous, having a clear understanding of ordinary recovery serves to better appreciate the variability imposed by the injury to cortical activity and behavior. Thus, we will identify how damaged neural circuits affect established cortical activity pathways and dynamics that underlie behavior recovery. The proposed studies are thus significant because they will establish the mechanistic correspondence, examining activation of neural pathways and their dynamics linked to habitual and intentional behaviors that reveal novel, medically relevant biomarkers that promote a robust inference of arousal states during emergence from anesthesia and after brain injury.", "keywords": [ "Affect", "Anesthesia procedures", "Anesthetics", "Animals", "Anterior", "Area", "Arousal", "Auditory", "Automobile Driving", "Awareness", "Behavior", "Behavioral", "Biological Assay", "Biological Markers", "Brain", "Brain Injuries", "Brain Stem", "COVID-19 survivors", "Cell Nucleus", "Coma", "Conscious", "Consciousness Disorders", "Cues", "Decerebration procedure", "Deglutition", "Diabetic Coma", "Doppler Ultrasound", "Exhibits", "Face", "Goals", "Head", "Hour", "Image", "Individual", "Inhalation", "Injury", "Knowledge", "Learning", "Link", "Lip structure", "Maps", "Measurement", "Measures", "Mediating", "Medical", "Methods", "Modeling", "Monitor", "Motor", "Motor Activity", "Motor Cortex", "Movement", "Mus", "Neural Pathways", "Neurons", "Pathologic", "Pathway interactions", "Patients", "Pattern", "Persons", "Population", "Population Dynamics", "Preparation", "Process", "Prognosis", "Prosencephalon", "Public Health", "Quality of life", "Recovery", "Reflex action", "Reporting", "Rodent", "Signal Transduction", "Silicon", "Stimulus", "System", "Techniques", "Time", "Touch sensation", "Ultrasonography", "Unconscious State", "Wakefulness", "Water", "Work", "auditory stimulus", "basal forebrain", "behavioral response", "deep learning", "density", "experimental study", "extracellular", "frontal lobe", "goal oriented behavior", "imaging system", "improved", "innovation", "kinematics", "motor behavior", "neural", "neural circuit", "neuromechanism", "novel", "optogenetics", "recruit", "response", "restoration", "sensory stimulus", "sound", "temporal measurement", "tongue root" ], "approved": true } }, { "type": "Grant", "id": "11709", "attributes": { "award_id": "1K99NS133961-01", "title": "Neurobiological Mechanisms of Fatigue in Health and after COVID-19", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 10999, "first_name": "Vicky R", "last_name": "Whittemore", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2025-06-30", "award_amount": 99113, "principal_investigator": { "id": 27579, "first_name": "Agostina", "last_name": "Casamento Moran", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2039, "ror": "", "name": "HUGO W. MOSER RES INST KENNEDY KRIEGER", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Fatigue is one of the most common and debilitating symptoms in neurological, psychiatric, and other chronic illnesses; however, it remains poorly understood and undertreated. Post-acute sequelae of SARS-CoV-2 infection (PASC) is a novel syndrome characterized by a range of symptoms present four or more weeks after the acute phase of COVID-19. Among these symptoms, severe fatigue is the most common and debilitating. Critical hurdles to understanding and treating fatigue include its multidimensional nature and the lack of quantitative methods to characterize it. In this MOSAIC K99/R00 application, I propose to use a novel `fatigue paradigm' that leverages neuromuscular, neuroeconomic, and computational methods to objectively investigate the neurobiological mechanisms of three features of fatigue in healthy individuals and individuals with PASC: feeling of weariness (how weary one feels), sense of effort (how one perceives a previously exerted force), and willingness to exert effort (an individual's decision to engage in effortful actions). My central hypothesis is that fatigue is comprised of at least three separable features, which represent distinct psychophysiological aspects, have unique neural correlates, and are differentially affected by PASC. The experiments proposed for the K99 Phase, which will be executed in Dr. Vikram Chib's Neuroeconomic Laboratory in the Kennedy Krieger Institute and Department of Biomedical Engineering at Johns Hopkins, will identify the brain network(s) encoding the features of fatigue in healthy individuals (Aim 1) and investigate how fatigue manifests in individuals with PASC (Aim 2). Through these projects, and the guidance of my mentoring team (Drs. Vikram Chib, Karen Quigley, Laura Malone, and Martin Lindquist), I will acquire complementary expertise in neuroimaging, psychophysiology, and computational and translational neuroscience. In the R00 Phase, I propose to merge my expertise in neuromuscular physiology and motor control with my newly acquired skills to identify the brain network(s) encoding fatigue in PASC (Aim 3). This Phase will be executed in my own laboratory upon securing an independent faculty position. The current epidemiological significance of fatigue and PASC makes this proposal especially timely and important, as it will significantly advance our understanding of fatigue and contribute to the NIH's RECOVER initiative. Further, the proposed research and training plans will allow me to accomplish my long-term career goal of becoming an independent investigator who will distinguish the neurobiological mechanisms of fatigue in different illnesses and develop targeted clinical interventions.", "keywords": [ "Acute", "Affect", "Affective", "Age", "Behavioral", "Biofeedback", "Biomedical Engineering", "Brain", "COVID-19", "Chronic Disease", "Clinical", "Computing Methodologies", "Data", "Decision Making", "Development Plans", "Dimensions", "Economic Burden", "Epidemiology", "Exhibits", "Faculty", "Fatigue", "Feeling", "Foundations", "Future", "Goals", "Health", "Healthcare Systems", "Individual", "Intervention", "Isometric Exercise", "Laboratories", "Learning", "Magnetic Resonance Imaging", "Measures", "Mentors", "Methods", "Muscle", "Nature", "Neurologic", "Participant", "Patient Self-Report", "Phase", "Physiology", "Positioning Attribute", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Psychophysiology", "Race", "Research", "Research Personnel", "SARS-CoV-2 infection", "Secure", "Symptoms", "Syndrome", "Techniques", "Training", "United States", "United States National Institutes of Health", "career", "career development", "common symptom", "computational neuroscience", "disabling symptom", "experimental study", "motor control", "neural correlate", "neurobiological mechanism", "neuroeconomics", "neuroimaging", "neuromuscular", "novel", "prevent", "response", "sex", "skill acquisition", "skills", "translational neuroscience", "willingness" ], "approved": true } }, { "type": "Grant", "id": "11710", "attributes": { "award_id": "1I01BX005651-01A2", "title": "Establishing the Therapeutic Efficacy of Alpha-1-Antitrypsin and Enoxaparin Against 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": "2023-07-01", "end_date": "2027-06-30", "award_amount": null, "principal_investigator": { "id": 27580, "first_name": "EDWARD D", "last_name": "CHAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1828, "ror": "https://ror.org/04d7ez939", "name": "VA Eastern Colorado Health Care System", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "The clinical outcome for patients with severe COVID-19 remains poor due to the lack of highly efficacious treatment for such individuals. Finding a better remedy for them is an important niche and immediate unmet need. The aim of this pre-clinical project is to substantiate the therapeutic effect of combined alpha-1- antitrypsin (AAT) + enoxaparin (a low molecular weight heparin) against SARS-CoV-2 infection and its consequences. Establishing the efficacy of AAT + enoxaparin combination will provide a necessary foundation for future clinical trials with the goal of employing effective therapy for those with severe COVID-19. We have novel biological evidence supported by Artificial Intelligence-based molecular modeling that enoxaparin synergizes with AAT to inhibit TMPRSS2 (a cell surface protease that activates the spike protein of SARS-CoV-2) and to reduce SARS-CoV-2 burden in primary human airway epithelial cells (hAEc) and monocyte-derived macrophages (MDM). Because both AAT and enoxaparin embrace a panoply of activities that antagonize other pathogenic mechanisms of severe COVID-19 – including anti-inflammatory, anti-thrombotic, pro-autophagy (known to kill MERS-CoV), and endothelial cell protection – we hypothesize that the AAT + enoxaparin combination will be most effective (compared to each alone) in mitigating SARS- CoV-2 infection and its consequences. We will use three complementary models to elucidate the efficacy of AAT, enoxaparin, and combination of both against SARS-CoV-2 infection: (i) primary hAEc since they express high ACE2 levels, fulminant airway disease occurs, and infection of ciliated hAEc and breach of their defense initiates a portal of entry into the lower airways / alveoli to cause COVID-19 pneumonia; (ii) MDM + plasma derived from AAT-deficient individuals immediately before and immediately after receiving routine intravenous AAT since macrophages are key orchestrators of the hyper-inflammatory response seen with COVID-19; and (iii) two murine models, one with wildtype AAT and another with AAT knocked out. Aim 1: Determine in primary hAEc the mechanisms by which AAT, enoxaparin, and both reduce SARS- CoV-2 infection and its consequences. Approach: hAEc will be infected with SARS-CoV-2 followed by no treatment or treatment with AAT, enoxaparin, or combination of both and assayed for viral load, autophagic flux, pro-inflammatory cytokines, and hAEc viability and barrier integrity. Aim 2: Determine in macrophages the mechanisms by which AAT (given in vivo) ± enoxaparin mitigate SARS-CoV-2 infection. Approach: infect human MDM cultured in autologous plasma – prepared from AAT- deficient individuals before and after AAT infusions ± ex vivo enoxaparin – with SARS-CoV-2 and determine viral load, autophagic flux, and pro-inflammatory cytokine / macrophage extracellular trap (METs) production. Aim 3: Determine if SARS-CoV-2 infection of mice is mitigated by AAT, enoxaparin, and combination of both. Approach: transgenic (Tg) mice bred to express human ACE2 with or without deletion of AAT (to represent humans who are AAT-replete and AAT-deficient, respectively) will either be left untreated or treated with AAT, enoxaparin, or the combination along with SARS-CoV-2 infection. From the lungs and spleens, we will quantify viral load and the phenotypes of macrophages, dendritic cells, CD4+ T cells, and CD8+ T cells in both organs, as well as analyze the lungs for epithelial and endothelial injury, co-localization of SARS-CoV-2 with airway and alveolar epithelial cells, and neutrophil extracelluar trap (NETs) formation (both METs and NETs implicated in immunothrombosis of severe COVID-19). Establishing the efficacy of AAT + enoxaparin combination will provide a foundation for future clinical trials with the goal of employing more effective therapy for veterans and non-veterans with severe COVID-19.", "keywords": [ "2019-nCoV", "ACE2", "Airway Disease", "Alveolus", "Anti-Inflammatory Agents", "Artificial Intelligence", "Autologous", "Autophagocytosis", "Biochemical", "Biological", "Biological Assay", "Blood Vessels", "Breeding", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "COVID-19", "COVID-19 impact", "COVID-19 pneumonia", "Cell Survival", "Cell surface", "Cells", "Clinical", "Clinical Trials", "Cytoprotection", "Data", "Dendritic Cells", "Endothelial Cells", "Endothelium", "Enoxaparin", "Enzymes", "Epithelial", "Epithelial Cells", "Foundations", "Future", "Goals", "Human", "Individual", "Infection", "Inflammatory", "Inflammatory Response", "Inflammatory Response Pathway", "Infusion procedures", "Injury", "Intravenous", "Knock-out", "Left", "Low-Molecular-Weight Heparin", "Lung", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Mus", "Organ", "Pathogenicity", "Patient-Focused Outcomes", "Peptide Hydrolases", "Phenotype", "Plasma", "Pre-Clinical Model", "Production", "Property", "Proteins", "SARS-CoV-2 infection", "SARS-CoV-2 inhibitor", "SARS-CoV-2 spike protein", "Safety", "Spleen", "TMPRSS2 gene", "Testing", "Therapeutic Effect", "Thrombosis", "Transgenic Mice", "Treatment Efficacy", "Veterans", "Viral Load result", "Virus", "airway epithelium", "alpha 1-Antitrypsin", "alpha 1-Antitrypsin Deficiency", "alveolar epithelium", "antagonist", "cell injury", "cell type", "cytokine", "cytotoxicity", "effective therapy", "efficacious treatment", "extracellular", "immunothrombosis", "in vivo", "macrophage", "molecular modeling", "monocyte", "mouse model", "neutrophil", "novel", "pre-clinical", "prevent", "severe COVID-19", "synergism", "therapeutic evaluation", "thrombotic" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1392, "count": 13920 } } }