Longitudinal Immunological Impact of SARS-CoV-2 Infection

SARS-CoV-2 感染的纵向免疫学影响

• 批准号: 10265644
• 负责人: Timothy Jensen Henrich
• 金额: $ 73.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265644
• 关键词: 2019-nCoV; Academic support; Address; Adult; Antibody Response; Biotechnology; Blood Cells; Blood Plasma Volume; CD8-Positive T-Lymphocytes; COVID-19 diagnosis; COVID-19 severity; Clinical; Communities; Consent; Convalescence; Databases; Development; Diagnostic; Disease; Enrollment; Foundations; Funding; Goals; HIV; Humoral Immunities; Immune response; Immunity; Immunologics; Immunology; Immunotherapy; Individual; Infection; Informed Consent; Kinetics; Lead; Longitudinal cohort; Maintenance; Medical; Mononuclear; Morbidity - disease rate; Participant; Peripheral Blood Mononuclear Cell; Pharmacologic Substance; Plasma; Process; Protocols documentation; Recording of previous events; Recovery; Research; Research Personnel; SARS-CoV-2 infection; Saliva; Secure; Severities; Symptoms; T cell response; T-Lymphocyte; Viral; adaptive immunity; cohort; comorbidity; demographics; design; improved; interest; mortality; novel coronavirus; pandemic disease; peripheral blood; recruit; response; vaccine development; virology

SARS-CoV-2 disease has recently become a major pandemic with significant global morbidity and mortality. Several key questions regarding the durability of immune responses to SARS-CoV-2 remain unanswered, such as how long protective humoral and adaptive immunity persist following mild to more severe disease, and whether or not the immune response may lead to longer-term protection from re-infection. As a result, there is urgent need to develop long-term, longitudinal cohorts that include a wide spectrum of SARS-CoV-2 infection severity and appropriately matched uninfected controls to study such questions. As a result, we initiated the Long-term Impact of Infection with Novel Coronavirus (LIINC) study leveraging our expertise at UCSF with longitudinal cohort design and implementation for HIV and other infections, to identify and collect largevolumes of peripheral blood and saliva during frequent intervals starting during the early convalescent period. Building on our strong collaborative expertise in cohort implementation, virology and immunology, we will recruit and characterize adults with a range of initial SARS-CoV-2 disease severity (asymptomatic to severe) and matched, uninfected controls. We have two short-term, high-impact objectives that we expect to address rapidly, once funding is secured. First, we will obtain, process, and rapidly distribute large numbers of PBMCs and large volumes of plasma, serum and saliva for collaborative research to improve SARS-CoV-2 diagnosis and treatment. We expect to achieve this objective rapidly as we have an existing protocol, consent process, database and all of the required SOPs. We also have an established referral network already in place and expect to rapidly enroll the cohort given intense community interest. Leveraging our nearly 20 year history, we have designed a protocol and informed consent process that will allow us to rapidly support academic groups, foundations, and biotechnology and pharmaceutical companies to develop diagnostics and therapies. Second, using an extensive team of local investigators, we will characterize the establishment and decay adaptive and humoral immune response to SARS-CoV-2. More specifically, our aims are to expand the LIINC cohort to collect large volumes of plasma, serum and saliva at frequent intervals from early disease convalescence (21 days following initial symptoms) to 24 months after recovery, determine the impact of SARS-CoV-2 infection on viral-specific CD4 and CD8 T cell responses up to 24 months following onset of symptoms, and define the long-term kinetics of the antibody response and the duration of protective immunity following infection with SARS-CoV-2. Together, results from our studies would have implications on duration of protective immunity and provide key information on immunotherapy and vaccine development.

SARS-CoV-2 疾病最近已成为一种重大流行病，具有显着的全球发病率和死亡率。 关于 SARS-CoV-2 免疫反应持久性的几个关键问题仍未得到解答，例如 轻度至重度疾病后，保护性体液免疫和适应性免疫能持续多久，以及 免疫反应是否可以带来更长期的保护，防止再次感染。结果，有 迫切需要开发涵盖广泛 SARS-CoV-2 感染的长期纵向队列 严重程度和适当匹配的未感染对照来研究此类问题。结果，我们发起了 新型冠状病毒感染的长期影响 (LIINC) 研究利用我们在 UCSF 的专业知识 针对艾滋病毒和其他感染的纵向队列设计和实施，以识别和收集大量样本 从恢复期早期开始，定期采集外周血和唾液。 凭借我们在队列实施、病毒学和免疫学方面强大的合作专业知识，我们将 招募并表征具有一系列初始 SARS-CoV-2 疾病严重程度（无症状到严重）的成年人 以及匹配的、未感染的对照。我们希望实现两个短期、高影响力的目标 一旦资金到位，就可以迅速开展工作。首先，我们将获取、处理并快速分配大量的PBMC 以及大量血浆、血清和唾液，用于合作研究以改善 SARS-CoV-2 诊断 和治疗。我们希望迅速实现这一目标，因为我们有现有的协议、同意流程、 数据库和所有必需的 SOP。我们还建立了一个已建立的推荐网络，并且 鉴于社区的强烈兴趣，预计会迅速招募该群体。凭借我们近20年的历史，我们 设计了一个协议和知情同意流程，使我们能够快速支持学术团体， 基金会、生物技术和制药公司开发诊断和治疗方法。第二， 利用一个由当地调查人员组成的广泛团队，我们将描述建立和衰变的适应性和 针对 SARS-CoV-2 的体液免疫反应。更具体地说，我们的目标是将 LIINC 群体扩展到 从疾病早期恢复期开始，定期收集大量血浆、血清和唾液（21 最初症状后的几天）到康复后 24 个月，确定 SARS-CoV-2 感染对 症状出现后长达 24 个月的病毒特异性 CD4 和 CD8 T 细胞反应，并定义 抗体反应的长期动力学和感染后保护性免疫的持续时间 SARS-CoV-2。总之，我们的研究结果将对保护性免疫的持续时间产生影响 并提供免疫疗法和疫苗开发的关键信息。