Longitudinal Immunological Impact of SARS-CoV-2 Infection

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, suchas how long protective humoral and adaptive immunity persist following mild to more severe disease, andwhether or not the immune response may lead to longer-term protection from re-infection. As a result, there isurgent need to develop long-term, longitudinal cohorts that include a wide spectrum of SARS-CoV-2 infectionseverity and appropriately matched uninfected controls to study such questions. As a result, we initiated theLong-term Impact of Infection with Novel Coronavirus (LIINC) study leveraging our expertise at UCSF withlongitudinal cohort design and implementation for HIV and other infections, to identify and collect large-volumes 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 willrecruit 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 addressrapidly, once funding is secured. First, we will obtain, process, and rapidly distribute large numbers of PBMCsand large volumes of plasma, serum and saliva for collaborative research to improve SARS-CoV-2 diagnosisand 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 andexpect to rapidly enroll the cohort given intense community interest. Leveraging our nearly 20 year history, wehave 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 andhumoral immune response to SARS-CoV-2. More specifically, our aims are to expand the LIINC cohort tocollect large volumes of plasma, serum and saliva at frequent intervals from early disease convalescence (21days following initial symptoms) to 24 months after recovery, determine the impact of SARS-CoV-2 infection onviral-specific CD4 and CD8 T cell responses up to 24 months following onset of symptoms, and define thelong-term kinetics of the antibody response and the duration of protective immunity following infection withSARS-CoV-2. Together, results from our studies would have implications on duration of protective immunityand provide key information on immunotherapy and vaccine development.