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

• 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
• 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

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系统综合征冠状病毒2型（SARS-CoV-2）的到来，这是COVID-19的病原体。SARS-CoV-2感染表现出一系列症状，从无症状到不适、肌痛和咳嗽。大约15%的患者将继续发展为与肺炎特征一致的严重疾病，伴有低氧血症和胸部CT扫描上的多叶毛玻璃样阴影。许多患有严重疾病的患者将需要ICU护理，发展为急性呼吸窘迫综合征（ARDS），休克，多系统器官衰竭和双重感染。可能需要体外膜肺氧合（ECMO）来维持生命。来自美国和中国的初步估计发现，年龄较大和慢性阻塞性肺病（COPD）、缺血性心脏病、糖尿病和免疫抑制等基础合并症与COVID-19死亡率增加相关。然而，发病率和死亡率也可能发生在年轻患者中。虽然抗病毒药物正在随机对照试验中进行研究，但在对照临床试验之外越来越多地使用标签外宿主和病原体导向疗法，并且几乎没有科学证据支持其使用。这里提出的研究是“一项前瞻性队列研究，旨在评估新冠肺炎住院患者的纵向免疫反应”。本研究是一项由NIH NIAID过敏、免疫学和移植部协调的多中心研究。该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COVID-19及其后遗症的临床下降与消退相关的措施。这些研究对于确定潜在靶点和宿主导向治疗干预的时机至关重要。了解与临床疾病相关的宿主免疫反应动力学和表型将有助于优先考虑宿主靶向干预和治疗试验，以限制或缓解疾病进展和疾病恢复。OHSU作为一个研究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，该研究将前瞻性收集临床、实验室和放射学患者数据，并与血液样本和呼吸道分泌物的收集相协调，以确定住院患者疾病谱中COVID-19的免疫表型和基因组特征。随后将对受试者进行感染后长达一年的随访，包括间隔病史、标本采集和分析。这项研究的结果预计将有助于优先考虑干预措施和/或优化宿主反应导向疗法的给药时机