Immune perturbations induced by SARS-CoV2 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; 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 (ISG ^hi ) state including: (i) CD14 ⁺ monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISG ^hi naïve CD4 ⁺ T cells, (iii) ISG ^hi proliferating cytotoxic CD8 ⁺ T cells, and (iv) ISG ^hi naïve and transitional B cells. Concurrently, we observed increased serum concentrations of both interferons and inflammatory cytokines in infected infants. Antibody responses to SARS-CoV-2 were also consistently detected in the absence of anti-IFN autoantibodies. Compared with infected adults, infants displayed a similar ISG signature in monocytes but a markedly enhanced ISG signature in T and B cells. These findings provide new 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.