Post-Acute COVID Sequelae in African Green Monkeys

非洲绿猴的急性新冠后遗症

基本信息

批准号：
10400464
负责人：
L Lee HAMM
金额：
$ 50万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10400464
关键词：
2019-nCoV Acclimatization Acute Address Affect African Green Monkey Animal Model Animals Autopsy Behavioral Bioavailable Biological Brain COVID-19 COVID-19 pandemic COVID-19 severity COVID-19 vaccine Cardiovascular Abnormalities Cardiovascular Diseases Caring Case Study Cathepsin L Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Chest Chronic Kidney Failure Clinical Collaborations Coughing Country Cytokine Activation Development Diabetes Mellitus Diagnosis Disease Disease Outbreaks Drug Targeting Early Diagnosis Elderly Environment Epithelial Exhibits FDA Emergency Use Authorization Fatigue Fogs Headache Health Hospitalization Human Hypertension Immune system Immunologic Adjuvants Immunologics Individual Infection Inflammation Intensive Care Units Intestinal permeability Investigation Kidney Laboratories Long COVID Long-Term Effects Lung Measurement Medical Mental Depression Modeling Morbidity - disease rate Mucous Membrane Nose Obesity Oral Outpatients Oxygen Pain Pathogenesis Patient Self-Report Patients Persons Pharmaceutical Preparations Pharyngeal structure Phase Plethysmography Prevention Production Property Protease Inhibitor Pulmonary Pathology Reducing Agents Research Residual state Resolution SARS-CoV-2 infection Safety Severities Shortness of Breath Sleep Disorders Smell Perception Study models Supplementation Surveys Swab Symptoms Taste Perception Telemetry Therapeutic Time Vaccination Vaccine Production Vaccines Variant Virus Virus Diseases Virus Shedding Washington acute infection arm biosafety level 3 facility body system carboxypeptidase C coronavirus disease effective therapy experience follow-up inhibitor/antagonist microbial mortality nasal swab neurobehavioral neutralizing antibody nonhuman primate novel organ growth persistent symptom prevent rectal severe COVID-19 systemic inflammatory response therapeutic vaccine vaccine development vaccine distribution vaccine hesitancy viral detection virology

项目摘要

PROJECT SUMMARY The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has resulted in global morbidity and mortality of dramatic proportions. Although the development of vaccines has occurred at an extremely rapid pace, significant challenges remain including vaccine hesitancy, the development of new variants, and major new outbreaks within several countries, despite best efforts for vaccine production and deployment. In addition, there is an urgent need to be able to address the post-acute sequelae of COVID-19 (PASC) or long haul COVID. Significant health problems, including neurobehavioral, pulmonary, renal, and cardiovascular abnormalities have been observed in both hospitalized and non-hospitalized patients well beyond the acute phase of infection, where replication competent virus is no longer shed. In studies proposed here, we will establish a model for the investigation of the longer-term effects of SARS-CoV- 2 infection in African green monkeys (AGM) supported by our previous observations during the acute phase of infection. In the context of our research strategy, we will perform clinical, biologic, immunologic, virologic, behavioral, pulmonary (plethysmography) and telemetric studies at baseline and during the course of our studies. The first six weeks of SARS-CoV-2 infection will be investigated within our Regional Biocontainment Laboratory at BSL- 3. At six weeks post-infection, we will evaluate the status of active and transmissible infection to support the safe transfer of animals to a BSL-2+ environment for an additional 12 weeks, where we will study the longer-term consequences of SARS-CoV-2 infection. Necropsies will be performed within BSL-3 as a safety precaution. Considerable anecdotal and survey evidence suggests vaccination of persons with PASC symptoms can be mitigated in whole or in part by the administration of vaccines approved under emergency use authorization. Our studies will investigate the administration of the Pfizer vaccine to animals two days post-infection to determine its potential as a therapeutic vaccine to modulate the acute and post-acute infection phases. We will also evaluate the potential of a Cathepsin-L inhibitor that interferes with cell entry of SARS-CoV-2 infection. Our previous collaborative studies with Selva Therapeutics, Inc, suggests virological and immunologic properties with earlier detection of neutralizing antibodies in AGM. We anticipate the proposed studies may provide urgently needed novel, translatable, and actionable approaches for the modulation of COVID-19 disease in humans.

项目概要严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 大流行已导致全球发病率和死亡率达到惊人的比例。尽管疫苗的研制进展迅速速度极快，仍然存在重大挑战，包括疫苗犹豫、新药物的开发尽管尽了最大努力进行疫苗生产和部署。此外，迫切需要能够解决 COVID-19 的急性后遗症 (PASC) 或长途 COVID。重大健康问题，包括神经行为、肺、肾和在住院和非住院患者中都观察到心血管异常感染的急性期，具有复制能力的病毒不再脱落。在此提出的研究中，我们将建立一个模型来调查 SARS-CoV-的长期影响 2 非洲绿猴（AGM）感染，得到我们之前在急性期观察的支持感染。在我们的研究策略范围内，我们将进行临床、生物学、免疫学、病毒学、行为学、基线和研究过程中的肺部（体积描记法）和遥测研究。第一个六周的 SARS-CoV-2 感染将在我们 BSL 的区域生物防护实验室内进行调查 3. 感染后六周，我们将评估活动性和传染性感染的状态，以支持安全将动物转移到 BSL-2+ 环境中另外 12 周，我们将在其中研究长期情况 SARS-CoV-2 感染的后果。作为安全预防措施，尸检将在 BSL-3 内进行。大量轶事和调查证据表明，有 PASC 症状的人可以接种疫苗通过管理紧急使用授权批准的疫苗可以全部或部分缓解。我们的研究将调查感染后两天对动物注射辉瑞疫苗的情况，以确定它作为调节急性和急性感染后阶段的治疗性疫苗的潜力。我们也会评估组织蛋白酶-L 抑制剂干扰 SARS-CoV-2 感染细胞进入的潜力。我们的之前与 Selva Therapeutics, Inc 的合作研究表明， AGM 中中和抗体的早期检测。我们预计拟议的研究可能会紧急提供需要新颖、可转化且可操作的方法来调节人类的 COVID-19 疾病。