Longitudinal Immunological Impact of SARS-CoV-2 Infection

SARS-CoV-2疾病最近已成为一种具有显著全球发病率和死亡率的重大流行病。 关于SARS-CoV-2免疫反应持久性的几个关键问题仍然没有答案，例如 在轻微到严重的疾病之后，保护性体液免疫和适应性免疫持续多久，以及 无论免疫反应是否可能导致对再次感染的长期保护。因此，有 迫切需要发展长期的纵向队列，包括广泛的SARS-CoV-2感染 严重程度和适当匹配的未感染对照来研究这样的问题。因此，我们发起了 利用加州大学旧金山分校的专业知识进行的新型冠状病毒(LIINC)感染的长期影响研究 艾滋病毒和其他感染的纵向队列设计和实施，以识别和收集大量病毒 从康复期早期开始，在频繁的间歇期间采集外周血液和唾液。 基于我们在队列实施、病毒学和免疫学方面的强大合作专业知识，我们将 招募和鉴定具有一系列初始SARS-CoV-2疾病严重程度(无症状到严重)的成年人 和配对的、未感染的对照组。我们有两个短期、高影响的目标，我们希望解决这两个目标 一旦获得资金，就会迅速采取行动。首先，我们将获得、加工和快速分发大量的PBMC 以及大量的血浆、血清和唾液用于合作研究，以改善SARS-CoV-2的诊断 和治疗。我们希望迅速实现这一目标，因为我们有一个现有的议定书，同意程序， 数据库和所有必需的SOP。我们也已经建立了转介网络，并且 考虑到社区的强烈兴趣，预计很快就会招募到这个队列。利用我们近20年的历史，我们 设计了一项协议和知情同意程序，使我们能够迅速支持学术团体， 基金会、生物技术和制药公司共同开发诊断和治疗方法。第二, 利用一支广泛的当地调查团队，我们将描述建立和衰落的适应性和 SARS-CoV-2的体液免疫应答。更具体地说，我们的目标是将LIINC队列扩大到 从疾病的早期康复开始，定期收集大量的血浆、血清和唾液(21 最初症状后的几天)到康复后的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 猪瘟病毒感染后抗体反应和保护性免疫持续时间的长期动态 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。 并提供有关免疫治疗和疫苗开发的关键信息。

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.