The adaptive immune responses to SARS-CoV-2 as a recall response susceptible to immune imprinting

One possible determinant of COVID-19 severity is immune imprinting (IP) by Common Cold Coronavirus (CCCV). As IP occurs only in recall immune responses, we investigated the immune response to SARS-CoV-2 in a cohort of unvaccinated individual to determine whether their immune response aligned with the primary or recall immune response patterns. Analysis of the Ig isotype response trajectories to the Mpro, NP, and S structural proteins and the S RBD in this group of 191 patients and 44 controls revealed a pattern of recall response in 94.2 % of cases. The levels of antibodies correlated positively with the severity of the condition rather than a milder course. High-resolution flow cytometry of fresh PBMNCs showed trajectories of plasmablasts, B cell subsets, and cTfh, suggesting a recall response. The transcriptomic profile demonstrated that this group was directly comparable to other contemporary cohorts. Overall, these findings support the idea that the response to SARS-CoV-2 is, in most cases, a recall response, likely due to B and T memory cells to CCCV, and therefore susceptible to immune imprinting and antibody-dependent enhancement.