Wednesday, January 15, 2025
1/15/2025
ABSTRACT The SARS-CoV-2 virus, the causative agent of COVID-19, has infected a reported 13,810,247 persons globally as of July 16, 2020 with a mortality rate of 4.2%. In the State of Louisiana, over 7.3% of the 86,411 COVID-19 cases involve people living with cancer. Treatment with convalescent serum or plasma is currently widely used in the setting of experimental trials and ad hoc. Theoretically, convalescent plasma contains protective antibodies that neutralizes virus and mitigates its pathogenic effects. Yet, there remains a large gap in our understanding of the mechanisms that drive humoral and cellular immune responses and how these responses correlate with disease course and protection as well as the durability of those responses. Furthermore, there is a need for serological assays that measure these responses accurately for serodiagnosis and as correlates of immunity and protection. Without this knowledge, the true efficacy of convalescent plasma as therapy for COVID-19 and our understanding of the humoral immune response to SARS-CoV-2, especially in immunocompromised patients, will remain unknown. A central hypothesis of our proposal is that the humoral immune responses to SARS- CoV-2 is protective in the short-term but appears to lack durability. However, a second hypothesis is that some remnant of immunity will be retained which will prevent recurrence of COVID19 but not necessarily re-infection. The overall mission of the Tulane University Convalescent Antibody and Immunity Network (TUCAIN) is to characterize this response with respect to functionality and durability. We will achieve these goals by studying a diverse cohort of COVID-19 survivors and minimally sick seroconverters. Using serial blood collections, we will apply several immunological technologies to study the evolution and durability of the immune response over time. We will also correlate these responses to patient outcomes and disease pathogenesis using a “big data”, systems biology approach. An approach, such as the one we propose, will allow us to determine if COVID-19 survivors develop long- term, antibody-based protection and we can confirm if convalescent plasma has therapeutic potential. This research will allow us to identify new targets for medicines and vaccines, inform personalized treatment strategies such as those required by immunocompromised patients with cance or HIV infection, and to provide novel immunological algorithms applicable to a wide range of human pathogens.
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