Early and long term immunity following SARS-CoV-2 infection in humans

人类感染 SARS-CoV-2 后的早期和长期免疫力

基本信息

批准号：
10493555
负责人：
William Messer
金额：
$ 4.5万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10493555
关键词：
2019-nCoV Acute Acute Respiratory Distress Syndrome Address Adult Aedes African Age Antibodies Antibody titer measurement Antibody-mediated protection Antigens Antiviral Agents Attenuated Vaccines Blood specimen Brazil COVID-19 COVID-19 patient Caring Cells Centers for Disease Control and Prevention (U.S.)Cessation of life China Chronic Obstructive Pulmonary Disease Clinical Cohort Studies Collection Controlled Clinical Trials Coughing Country Cross-Sectional Studies Culicidae Data Dengue Development Diabetes Mellitus Disease Disease Outbreaks Disease Progression Dose Enrollment Extracorporeal Membrane Oxygenation Flavivirus Fostering Frequencies Genomics Glass Heterogeneity Human Hypersensitivity Hypoxemia Immune Immune response Immunity Immunologic Factors Immunology Immunophenotyping Immunosuppression Individual Infection Integration Host Factors Intervention Kinetics Knowledge Label Laboratories Life Lobar Long-Term Effects Malaise Mass Vaccinations Measures Memory B-Lymphocyte Mission Modeling Morbidity - disease rate Myalgia Myocardial Ischemia Nail plate National Institute of Allergy and Infectious Disease Organ failure Patients Phase I/II Clinical Trial Phenotype Pneumonia Policies Prospective Studies Prospective cohort study Public Health Randomized Controlled Trials Recommendation Recording of previous events Recovery Research Resolution Risk SARS-CoV-2 infection Safety Shock Site South Africa South America Symptoms Testing Therapeutic Therapeutic Human Experimentation Therapeutic Intervention Transplantation United States National Institutes of Health Vaccination Vaccine Antigen Vaccinee Vaccines Viral Viral Antibodies Viral Load result Viral Vaccines Viremia Virus Virus Replication X-Ray Computed Tomography Yellow Fever Vaccine Yellow fever virus ZIKA Zika Virus adaptive immune response antibody detection base burden of illness chest computed tomography cohort comorbidity critical period health organization immunogenicity innovation mortality neutralizing antibody nonhuman primate novel coronavirus pathogen post SARS-CoV-2 infection pressure prospective prototype radiological imaging recruit respiratory response sample collection secondary analysis seroconversion seropositive superinfection

项目摘要

A cluster of respiratory illness that emerged in December, 2019 in Wuhan China marked the arrival of novel coronavirus Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. SARS-CoV-2 infection presents with a spectrum of symptoms, ranging from asymptomatic, to malaise, myalgias, and cough. Approximately 15% of patients will go on to develop severe disease consistent with characterized by pneumonia, with hypoxemia and multi-lobar ground glass opacities on chest CT scan. Many of these patients with severe disease will require ICU care, develop Acute Respiratory Distress Syndrome (ARDS), shock, multisystem organ failure, and superinfections. Extra-corporeal membrane oxygenation (ECMO) may be required to sustain life. Preliminary estimates from the US and China find that older age and underlying co-morbidities such as Chronic Obstructive Pulmonary Disease (COPD), ischemic heart disease, diabetes mellitus, and immunosuppression are associated with increase mortality in COVID-19. However, morbidity and mortality may also occur in younger patients. While anti-viral agents are being studied in randomized controlled trials, there is increasing use of off-label host and pathogen-directed therapies outside of controlled clinical trials and with little to no scientific evidence supporting their use. The research proposed here is “a prospective cohort study to assess longitudinal immune responses in hospitalized patients with covid-19.” This study is a multi-site study coordinated through the NIH NIAID Division of Allergy, Immunology, and Transplantation. The study will use immunophenotyping of host factors that have the potential to predict viral clearance or risk of prolonged viral replication and measures associated with clinical decline versus resolution of COVID-19 and its sequelae. These studies are critical for identifying potential targets and timing for host-directed therapeutic interventions. Understanding host immune response kinetics and phenotypes as they relate to clinical illness will assist in prioritizing trials of host-targeted interventions and treatments to limit or mitigate disease progression and recovery from illness. OHSU is participating as one site in this observational multi-site cohort study of hospitalized COVID-19 patients that will prospectively collect clinical, laboratory, and radiographic patient data in coordination with collection of blood samples and respiratory secretions in order to identify immunophenotypic and genomic features of COVID-19 across the spectrum of disease in hospitalized patients. Subjects will subsequently be followed for up to a year post-infection with interval histories and specimen collection and analysis. Results of this research are expected to help to prioritize interventions and/or optimize timing for administration of host-response directed therapeutics

2019 年 12 月在中国武汉出现的一系列呼吸道疾病标志着新型冠状病毒严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 的到来，该病毒是 SARS-CoV-2 感染的病原体。具有一系列症状，从无症状到不适、肌痛和咳嗽，大约 15% 的患者会继续发展为以肺炎为特征的严重疾病，胸部 CT 扫描显示低氧血症和多肺叶磨玻璃影，许多患有严重疾病的患者需要 ICU 护理，出现急性呼吸窘迫综合征 (ARDS)、休克、多系统器官衰竭和重复感染。美国和中国的初步估计发现，老年人和慢性阻塞性肺病（COPD）等潜在的合并症可能需要 ECMO 来维持生命。缺血性心脏病、糖尿病和免疫抑制与 COVID-19 死亡率增加有关，然而，尽管随机对照试验正在研究抗病毒药物，但年轻患者的发病率和死亡率也可能增加。 -在对照临床试验之外标记针对宿主和病原体的疗法，并且几乎没有科学证据支持其使用。这项研究是“一项评估住院 covid-19 患者纵向免疫反应的前瞻性队列研究”。是一个由 NIH NIAID 过敏、免疫学和移植部门协调进行的多中心研究将使用宿主因素的免疫表型分析，这些因素有可能预测病毒清除或病毒复制延长的风险，以及与新冠病毒临床衰退与缓解相关的措施。 -19 及其后遗症对于确定针对宿主的治疗干预的潜在目标和时机至关重要，因为它们与临床疾病相关，因此了解宿主免疫反应动力学和表型将有助于确定针对宿主的干预试验的优先顺序。 OHSU 作为一个中心参与了这项针对住院 COVID-19 患者的观察性多中心队列研究，该研究将前瞻性地收集临床、实验室和放射学患者数据，并配合收集随后，研究人员将在感染后对受试者进行长达一年的跟踪记录，以收集患者的血液样本和呼吸道分泌物，以识别住院患者的各种疾病的免疫表型和基因组特征。这项研究预计帮助确定干预措施的优先顺序和/或优化宿主反应导向治疗的给药时机