SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults’ responses

Differences in immune profiles of children and adults with COVID-19 have been previously described. However, no systematic studies have been reported from infants hospitalized with severe disease. We applied a multidimensional approach to decipher the immune responses of SARS-CoV-2 infected infants (n=26; 10 subacute, 11 moderate and 5 severe disease; median age=1.6 months) and matched controls (n=14; median age=2 months). Single cell (scRNA-seq) profiling of PBMCs revealed substantial alterations in cell composition in SARS-CoV-2 infected infants; with most cell-types switching to an interferon-stimulated gene (ISGhi) state including: (i) CD14+ monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISGhi naïve CD4+ T cells, (iii) ISGhi proliferating cytotoxic CD8+ T cells, and (iv) ISGhi naïve and transitional B cells. We observe increased serum concentrations of both interferons and inflammatory cytokines in infected infants. Antibody responses to SARS-CoV-2 are also consistently detect in the absence of anti-IFN autoantibodies. Compared with infected adults, infants display a similar ISG signature in monocytes but a markedly enhanced ISG signature in T and B cells. These findings provide insights into the distinct immune responses to SARS-CoV-2 in the first year of life and underscore the importance of further defining the unique features of early life immunity. Single cell RNA-seq profiling (scRNA-seq) of PBMCs from 26 SARS-CoV-2 infected infants (n=26; 10 subacute, 11 moderate and 5 severe disease; median age=1.6 months) and matched controls (n=14; median age=2 months). pCoV40_cleaned_12062021.h5ad: AnnData object containing 40 samples from 26 infants with COVID-19 and 14 healthy controls (i.e. pediatric cohort or pCoV). This object was generated running the scanpy pipeline at: https://github.com/dnehar/Infants_Cov19 The pipeline includes doublet removal, filtering based on mitochondrial as well as batch effect correction using BBKNN. The number of cells included in the object is 203,402 cells. paCov_Tsang_harm_withSCs_12072021.h5ad: AnnData object containing 79 samples from 40 samples from the pediatric cohort (pCoV) and 39 samples from a publicly available adult COVID-19 cohort (aCoV; Tsang lab; GSE161918). The pipeline includes doublet removal, filtering based on mitochondrial as well as batch effect correction using Harmony. The number of cells included in the object is 408,281 cells. For the re-analysis of GSE161918, the samples of interest (COVID T0 and healthy controls, listed in the 'List_samples_GSE161918.txt') were selected from the seurat object (GSE161918_AllBatches_SeuratObj.rds.gz) at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161918 Submitter declares that the raw data will be available through dbGAP (phs002655.v1) due to patient privacy concerns.