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

Abstract

ABSTRACTOne 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.