MATERNAL AND NEONATAL IMMUNE SIGNATURES OF PRENATAL SARS-COV-2 INFECTION AND ITS ASSOCIATION WITH EARLY NEURODEVELOPMENT

Evidence from previous viral outbreaks, such as influenza A, highlights the impact of maternal infections on fetal neurodevelopment. Given COVID-19's high mortality and long-term neurological effects, researchers raise concerns regarding neurodevelopmental outcomes of prenatal SARS-CoV-2 exposure. Recent studies have found elevated maternal pro-inflammatory cytokine levels, DNA methylation changes, and alterations in specific immune cell populations in the peripheral blood of pregnant women with COVID-19. However, the most vulnerable developmental time window to a SARS-CoV-2 infection, as well as the role of the mother's immune system in protecting the child from potentially harmful effects on brain development, remains unclear. To investigate this, the SIGNATURE study aims at identifying prognostic immunological factors and immunological signatures associated with cognitive impairment in children of mothers infected with SARS-CoV-2 during pregnancy. We performed analysis of PBMCs and plasma samples from pregnant women and their newborns with or without exposure to SARS-CoV-2 infection at different trimesters. Using single-cell RNA sequencing, we compared gene expression and compositional changes in the immune cells of SARS-CoV-2 exposed mother-child pairs and healthy controls. We integrated our findings with clinical data, including longitudinal developmental and cognitive assessments to investigate potential associations between immunological changes and neurocognitive outcomes. Additionally, we analyzed the DNA methylation status and cytokines levels in the plasma of the same pairs to investigate long-term immune imprinting and changes in the immune secretome. Our study is the first of its kind and provides crucial insights into the long-term impact of SARS-CoV-2 exposure on children exposed to a maternal infection.