Epigenetic imprinting of infant immunity by prenatal SARS-CoV-2

The impact of prenatal SARS-CoV-2 exposure on the infant immune system remains obscure. Here, we performed a longitudinal multi-omics study on the blood samples from in utero SARS-CoV-2 exposed uninfected (SEU) and healthy infants, and investigated early life immune development and BCG vaccine induced innate responses. Immune profiling revealed increased CD4+ naïve T cells in SEU infants at birth which correlated with IL-7. The single-cell analysis revealed a higher B cell tolerance, reduced αβ T cell activation and diminished monocyte innate state among SEU infants with an epigenetic underpinning. At 6-month of life, SEU infants demonstrated diminished function i.e reduced αβ T cells adaptive and monocyte’s BCG-induced innate response. Cell-cell communication analysis showed that attenuated αβ T cell and monocyte responses were counterbalanced by epigenetically imprinted anti-viral γδ T cells. Together, these findings provide a landscape of dynamic immune development during early infancy following prenatal exposure, with potential implications for the formation of immune memory.