W151 - Mapping Immune Perturbations Associated with sars-cov-2 Infection in Infants

Asunción Mejías – MD, Department of Infectious Diseases, St. Jude Children’s Research Hospital; Zhaohui Xu – Department of Infectious Diseases – St. Jude Children’s Research Hospital; Radu Marches – THE JACKSON LABORATORY; Duygu ucar – associate professor, THE JACKSON LABORATORY; Jacques banchereau – CSO, Immunai; Virginia Pascual – MD, Drukier Institute for Children’s Health and Department of Pediatrics, Weill Cornell Medicine; Octavio Ramilo – MD, Department of Infectious Diseases, St. Jude Children’s Research Hospital

Abstract Text: Differences between COVID-19-induced immune alterations in adults and children have been previously described. However, no systematic immune profiling studies have been conducted in infants. We applied a multidimensional approach (single cell transcriptome, cytokine measurements and antibody titers), to decipher the immune responses in SARS-CoV-2 infected infants (n=26; 10 subacute, 11 moderate, and 5 severe; median [interquartile range] age: 1.63 [0.93-7.59] months) and matched healthy controls (n=14; 2.01 [1.86-4.28] months). Single cell (scRNA-seq) profiling of PBMCs revealed that severe COVID-19 in infants was associated with: (i) a prominent interferon-stimulated gene (ISG) signature involving many blood immune cell types, especially CD14+, CD16+ monocytes and CD4+ T cells, which contrasts with the attenuated ISG signature reported in adults with severe disease, (ii) a high frequency of CD14+ monocytes co-transcribing ISGs and inflammasome-related molecules; and (iii) an expansion of ISGhi proliferating cytotoxic CD8+ T cells. Serum cytokine analyses showed increased serum concentrations of inflammatory cytokines such as IL6 and IL8, but also IFN and IFN-induced cytokines such as CXCL10 and CXCL11. Antibody responses to SARS-CoV-2 were consistently detected in infants without evidence of anti-interferon autoantibodies. Comparison with adult scRNA-seq PBMC data revealed a markedly stronger ISG signature within T and B cells of infected infants. Steroid treatment was associated with the expansion of a subset of circulating CD14+ monocytes exhibiting CD163 and IL1R2, in both infant and adult patients. Our findings shed insight into the distinct immune responses to SARS-CoV-2 in the first year of life.