Longitudinal Immunological Impact of SARS-CoV-2 Infection

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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.