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月在武汉出现的一系列呼吸道疾病中国标志着新型冠状病毒严重急性呼吸综合征冠状病毒-2的到来，该病毒是新冠肺炎的病原体。SARS-CoV-2感染呈现一系列症状，从无症状到不适、肌痛和咳嗽。约15%的患者将继续发展为符合肺炎、低氧血症和胸部CT扫描的多叶毛玻璃样阴影的严重疾病。其中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叠感染。维持生命可能需要体外膜氧合(ECMO)。来自美国和中国的初步估计发现，高龄和潜在的并存疾病，如慢性阻塞性肺疾病、缺血性心脏病、糖尿病和免疫抑制与新冠肺炎死亡率的增加有关。然而，发病率和死亡率也可能发生在较年轻的患者中。虽然抗病毒药物正在进行随机对照试验研究，但在对照临床试验之外，越来越多地使用非标签宿主和病原体导向疗法，而且几乎没有科学证据支持它们的使用。这里提出的研究是“一项前瞻性队列研究，旨在评估住院的新冠肺炎患者的纵向免疫反应。”这项研究是一项由NIH NIAID过敏、免疫学和移植部门协调的多点研究。这项研究将使用宿主因素的免疫表型分析，这些因素可能预测病毒清除或病毒复制时间延长的风险，以及与新冠肺炎及其后遗症的临床下降和解决相关的措施。这些研究对于确定宿主指导的治疗干预的潜在靶点和时机至关重要。了解宿主免疫反应动力学和与临床疾病相关的表型将有助于优先进行宿主靶向干预和治疗的试验，以限制或减缓疾病的进展和疾病的恢复。卫理公会大学作为一个站点参与了这项针对住院新冠肺炎患者的观察性多地点队列研究，该研究将前瞻性地收集患者的临床、实验室和放射数据，同时收集血液样本和呼吸道分泌物，以确定住院患者各种疾病的新冠肺炎的免疫表型和基因组特征。随后将在感染后对受试者进行长达一年的跟踪，间歇性病史和标本收集和分析。这项研究的结果有望帮助确定干预措施的优先顺序和/或优化宿主反应导向疗法的给药时机