Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth

The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1). The immune response in blood was characterized by upregulation of activation markers on innate cells, no inflammatory cytokines, but several chemokines and IFNα. The latter correlated with viral load and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell multi-omics. Together, these data provide a snapshot of immunity to infection during the initial weeks and months of life. [Display omitted] •Infants and young children mount antibody responses that are durable for up to 300 days•Atypical innate response in blood: no inflammatory markers; high IFNα and chemokines•Robust upper respiratory tract antiviral and inflammatory responses•Single-cell transcriptomics and epigenomics in the first weeks and months of life Multi-omics analysis of blood and nasal samples from human infants and their mothers indicates strong and sustained immunity following SARS-CoV-2 infection during the initial months of life.