Human Immune repertoire and gene expression in pediatric and adult SARS-CoV-2 infected patients using single cell multi-omics approaches

Abstract

Abstract SARS-CoV-2 represents a global health crisis, yet major knowledge gaps remain about the human immune response against the virus infection and related treatment in both pediatric and adult patients. Immune repertoires (TCR and BCR) and related gene expression at massive single cell level play a crucial role in early-stage infection and late virus clearance. By using single cell multi-omics approaches, we analyzed immune repertoire and gene expression in 9 COVID-19 patients and 3 controls. We used single-cell mRNAseq and observed increased expression of inflammatory cytokines and transcription factors such as CXCL1, RNASE2, EGR1, CXCL2, and CXCL8 in either adult or pediatric COVID-19 infected patients compared to controls. Ten surface proteins such as CD62L, CD16, CD20, CD56, CD14, and CD45RA were quantitated by AbSeq. CD14+ cells were more prevalent in adult COVID-19 patients and CD3+ T cells were less prevalent. We conducted comparative analyses of TCR and BCR repertoire using single-cell V (D)J sequencing approach. The clonotypes were defined by using either combined alpha and beta chains or beta chains only. Distinct clonotypes were identified in both pediatric and adult COVID-19 patients. We did not see any significant clonotype expansion in this sample set yet but further analysis is warranted. The combination with the highest frequency in COVID-19 was TRAV29-TRBV27. Our study provides novel insights and bioinformatic analysis tools on immune repertoire in COVID-19.