ABSTRACT The devastating effects of the COVID-19 pandemic have reverberated through every aspect of our civilization. While SARS-CoV-2, the viral etiology of COVID-19, seems to spare infants in terms of actual infection, it is currently unknown whether maternal infection during pregnancy will have long-term effects on children born during the pandemic. A variety of prenatal insults, including infections and stress, are well-known to lead to increased risk of affective disorders in both mother and child. With its disproportionate reach into already disadvantaged minority communities, the impact of the COVID-19 pandemic on the dyad is currently unknown and potentially of unprecedented magnitude with enduring consequences for women's mental health and children's developmental origins of health and disease (DOHaD). The COVID-19 Mother Baby Outcome (COMBO) initiative, a large multidisciplinary collaborative, was established at Columbia University Irving Medical Center to follow SARS-CoV-2 exposed laboring mothers and their newborns and compare their long- term health outcomes to case-matched dyads without prenatal exposure. This proposal will follow a subset of the larger COMBO cohort to study socioemotional circuits (fronto-limbic) and behavior (caregiving and bonding) in 100 mother-child dyads from prepartum to 18 months postpartum. The team assembled to carry out this study consists of two provider scientists (Dumitriu, pediatrician and neuroscientist, & Monk, clinical psychologist embedded in Ob/Gyn) and neuroscientist/pediatric neuroimager (Marsh). Using an innovative dyadic approach, olfaction testing, multimodal MRI, wearable in-home physiological recordings, observational mother and child assessments (free play, routine care, Harvard Reactivity and Still Face paradigms), this proposal will test the overarching hypothesis that prenatal SARS-CoV-2 exposure affects (1) mother and (2) child brain and behavior, and (3) demonstrate that the socioemotional health of each member of the mother- child dyad is intrinsically related to that of the other. Detecting COVID-19-related early neurobehavioral effects on mothers and the next generation will provide insights into intervention strategies and contribute significantly to DOHaD and stress science.