Early immune events during SARS-CoV-2 infection impact memory T and B cell responses

Immune responses elicited by natural infection of the coronavirus SARS-CoV-2 (COVID-19) show significant heterogeneity in the magnitude and quality of memory T and B cell responses. However, little is known about the contributing factors. In this study, we investigated the early immune factors that contribute to this variability using RNA-seq, targeted proteomics, and flow cytometry analyses. Specifically, we sought to investigate associations between early immune responses and SARS-CoV-2 memory immunity in a longitudinal cohort of 46 individuals hospitalized for COVID-19 from May 2020 to March 2021. These participants returned for follow-up visits up to one-year post-hospitalization where we characterized antibody titers, antibody neutralization, antibody durability, and cellular memory T and B cell responses with multiple assays. Additionally, using integration analysis of Omic measurements, we identified common genes, proteins, and cellular pathways associated with differential memory response outcomes. Our data suggests that high levels of inflammatory proteins, and co-stimulatory molecules during the early stages of COVID-19 lead to enhanced memory T and B cell responses and improved durability. Alternatively, molecules that have a negative effect on dendritic cell maturation including TNFSF11 and FLT3LG correlated with suboptimal memory immune responses. Importantly, we were able to identify early markers that are positively and negatively associated with durable antibody responses in infected participants. This study provides a unique and thorough examination of both innate and memory immunity in the same patients over time, offering valuable insights into the long-term durability of SARS-CoV-2 immunity.