Post-Acute COVID Sequelae in African Green Monkeys

非洲绿猴的急性新冠后遗症

• 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
• 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

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.

项目摘要 严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）大流行导致全球 发病率和死亡率的比例惊人。虽然疫苗的开发已经发生在一个 尽管速度非常快，但仍然存在重大挑战，包括疫苗犹豫，新的 尽管为疫苗生产做出了最大努力， 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。严重的健康问题，包括神经行为、肺、肾和 在住院和非住院患者中均观察到心血管异常， 感染的急性期，此时具有复制能力的病毒不再脱落。 在这里提出的研究中，我们将建立一个模型，用于调查SARS-CoV的长期影响， 2感染非洲绿色猴（AGM）的支持，我们以前的观察，在急性期， 感染 在我们的研究策略的背景下，我们将进行临床，生物，免疫，病毒学，行为， 肺（体积描记法）和遥测研究在基线和在我们的研究过程中。第一 将在我们位于BSL的区域生物防护实验室内对SARS-CoV-2感染进行为期六周的研究， 3.在感染后六周，我们将评估活动性和传染性感染的状态，以支持安全的 将动物转移到BSL-2+环境中额外12周，在那里我们将研究长期 SARS-CoV-2感染的后果。作为安全预防措施，将在BSL-3内进行尸检。 相当多的轶事和调查证据表明，对有PASC症状的人进行疫苗接种可能是一种有效的方法。 通过接种经紧急使用授权批准的疫苗，可全部或部分缓解。我们 研究将调查辉瑞疫苗在感染后两天对动物的给药， 其作为治疗性疫苗调节急性和急性后感染阶段的潜力。我们还将 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 以前与Selva Therapeutics公司的合作研究表明， 早期检测AGM中和抗体。我们预计拟议的研究可能会紧急提供 需要新的、可转化的和可操作的方法来调节人类COVID-19疾病。