Single-cell analysis unravels the role of NK cells and monocytes in the control of SARS-CoV-2 breakthrough infections in vaccinated individuals.

Analyzing the antiviral response of natural killer (NK) cells and monocytes is essential to understanding vaccine protection in an immunized population facing SARS-CoV-2 variant breakthrough infections (BTIs). In this study, in peripheral blood mononuclear cells (PBMCs) from vaccinated individuals with SARS-CoV-2 infections, we observed an increase in adaptive CD57NKG2C NK cells and classical monocytes (CMs). Single-cell sequencing analysis showed that the transcriptomic profiles of IFN-induced IFIT3 and other IFN-stimulated genes exhibited marked upregulation in NK cells, defined as CD56CD57NKG2CIFIT3 NK cells. Additionally, CM in the blood showed characteristics indicative of differentiation into dendritic cells (DCs) and macrophages, which further evidenced their potential antiviral functions. Our study indicates that a vaccinated population rapidly activates an antiviral innate immune response following a BTI, thus revealing a link to the control of viral replication during SARS-CoV-2 BTIs.