Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period. Yu et al.

Understanding immune memory to Common Cold Coronaviruses (CCCs) impacts SARS-CoV-2 infection outcome, and is crucial for pan-corona vaccine development. With longitudinal pre-pandemic samples from 2016-2019, we assessed CCC-specific CD4+ T cell and antibody responses, comparing to other respiratory viruses and ubiquitous pathogens. CCC-specific memory CD4+ T cells were detected in most subjects, with comparable frequencies as other common antigens. Responses to CCC and other antigens sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ cell quantity and their magnitude did not correlate with yearly changes in CCC infection prevalence. Similarly, CCC-specific spike RBD-specific IgG responses were stable throughout the sampling period. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. The results suggest a steady and sustained CCC responses, likely from a stable pool of memory CD4+ T cells, instead of fast decaying responses by frequent reinfections.