Single-cell multi-omics analysis revealing immune features of inactivated SARS-CoV-2 vaccination in systemic lupus erythematosus patients

The COVID-19 vaccine-induced immunity has been widely reported in the general population, but the protective immune response of COVID-19 vaccines in SLE patients (SLEs) remains largely unknown. Here, we performed a comprehensive and time-series investigation of immunological alterations induced by inactivated COVID-19 vaccines in SLEs and healthy controls using single-cell multi-omics methods. Compared with healthy controls (HCs), the lower titres of neutralizing antibodies and global transcriptomic and epigenomic changes in peripheral immune cells were detected in SLEs. Increased expression levels of inflammatory responses related genes and AP-1 family members were commonly detected in SLEs and HCs, along with increased activation of T cells and diversity of T cell receptor repertoire. However, this vaccine enhanced chromatin accessibility at interferon response factors (IRF) loci in monocytes and conventional dendritic cells (cDCs) from SLEs at the late stage after vaccination, which was confirmed by transcriptome data and distinct from HCs. Vaccine induced less differentiations of B cells, expanded clonotypes and class switching clonotypes in SLEs, which was associated with impaired neutralization antibodies. Our study provides a system biology assessment of the transcriptomic and epigenomic landscape during an immune response induced by COVID-19 vaccine within SLEs, providing insights that will be useful in the optimization of vaccination strategies in immune compromised populations. We generated a single-cell multi-omics landscape for peripheral blood, including single-cell RNA sequencing (scRNA-seq), single-cell lymphocyte antigen receptor repertoire (single B/T cell receptor [BCR/TCR] sequencing), and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq). In this study, we collected single-cell data from four systemic lupus erythematosus patients and two health controls before (day 0) and after vaccination (day 28) using 10× Genomics platform. Due to human patient privacy concerns, the raw sequencing data have been deposited in Genome Sequence Archive (GSA) for Human under the accession number HRA004028.