Single cell multi-omic innate immune cell analysis reveals a SARS-CoV-2 specific monocyte phenotype

The use of single-cell multiomic technologies allows to dissect the heterogeneous host immune response during infections. In this study, a multiomic characterization of the innate immune compartment was performed by applying a high-throughput approach that enables the integrated analysis of transcriptome and proteome of the immune-repertoire at a single cell level in human HLADR-enriched peripheral blood mononuclear cells stimulated in vitro with SARS-CoV-2 variant Omicron BA.1. RNA-seq data derived from whole transcriptome and Ab-seq (BD Biosciences) libraries were filtered and analyzed by BD Seven Bridges software to identify differentially expressed genes (DEGs) at the single cell level in different subpopulations of monocytes, plasmacytoid dendritic cells (DC), conventional DC and NK cells. Pathways analyses with the identified DEGs were carried out too by inferring KEGG and Reactome databases. Gene ontology analysis revealed a complex regulation of cell processes and functions upon SARS-CoV-2 stimulation of innate cells: cytokine signaling, innate signaling and antiviral pathways, cell mobility and adherence, chemotaxis and antigen presentation. In particular, exposure to SARS-CoV-2 induces profound changes in monocyte physiology. By comparing results obtained upon treatment with live virus or with a TLR7/8 ligand, Resiquimod, mimicking a viral ssRNA, we found that stimulation with Omicron BA.1 SARS-CoV-2 variant strain induces a virus-specific phenotype in monocytes regulating differentiation status and impacting on expression of cell adhesion markers, cytokine and chemokine signaling molecules and antigen processing and presentation capacity. These results indicate that SARS-CoV-2 strongly affects host immune response by specifically altering monocyte functions and differentiation.