Infant Immunologic and Neurologic Development following Maternal Infection in Pregnancy during Recent Epidemics

Abstract/Summary The massive outbreak of newly emerged coronavirus disease 2019 (COVID-19) saw rapid global spread, leading to a pandemic infection and an unprecedented global health emergency. Just years before, we witnessed the devastating impact of Zika virus (ZIKV) to unborn fetuses in the Americas. This proposal responds to the need to fill critical gaps in the understanding of the clinical repercussions of antenatal infections such as ZIKV and SARS-CoV-2 infection in pregnant women to the developing immune system of their infants, through the evaluation of cellular and humoral immune responses and clinical and neurodevelopmental outcomes following maternal immune activation (MIA) in this vulnerable population. Our team of researchers has been collaborating over the last 7 years to characterize the clinical and cellular effects of in utero transmission of Zika virus (ZIKV), with the collection of specimens from over hundreds of mother- infant pairs from Brazil. We reported on multiple obstetrical and clinical outcomes of infants with congenital ZIKV infection in the literature, including that ZIKV vertical transmission rate is at least 65%, that infected children do not develop ZIKV specific neutralizing antibodies despite an early IgM response, and that maternal humoral immune responses tend to be robust with highly neutralizing activity. During the COVID-19 pandemic we established a cohort of mother-infant pairs at UCLA and Fiocruz, Rio de Janeiro and controls with mother-infant dyads enrolled to date in both places. We are utilizing the existing infrastructure and scientific methods developed in the aftermath of the ZIKV epidemic to further evaluate clinical, cellular humoral and inflammatory parameters predicting immunologic outcomes in infants and children exposed to either maternal ZIKV and SARS Cov2 infection. The main goal of the proposed research is to comprehensively characterize repercussions of MIA on infant immune development and clinical outcomes, with a focus on immune pathogenesis. We include a longitudinal cohort of 200 mother- infant pairs with COVID-19 and 100 healthy control mother-infant pairs in the US and Brazil and 200 mother-infant pairs with ZIKV in Brazil and 100 healthy control pairs at the same clinical sites to address these goals. This RO1 proposes to evaluate the repercussions of MIA on infant well- being and immune development. State of the art technology is used to address the scientific aims, with the research led by experts in the field of immunology, infectious diseases & congenital infections who have ongoing successful, productive partnerships. The data rendered will be crucial for the knowledge of immune pathogenesis in pediatric populations with antenatal viral exposures.