Triggered - Does Maternal COVID-19 Program an Exaggerated Immune Response in Neonates?

The consequences of gestational coronavirus disease 2019(COVID-19) exposure on neonatal immunity are incompletely understood. While vertical transmission to the fetus is rare, maternal COVID-19 exposure can adversely impact the neonate by inducing placental pathology, or indirectly, via neonatal immune programming. To investigate the latter, Gilley et al. analyzed cytokine levels in cord blood mononuclear cells (CBMCs) obtained from neonates exposed to chorioamnionitis, gestational COVID-19, and unexposed controls. They observed that fetal exposure to maternal inflammation, by either SARS-CoV-2 infection or chorioamnionitis, exaggerated the pro-inflammatory cytokine response to neonatal bacterial pathogens in cultured CBMCs. While both chorioamnionitis and COVID-19 exposure exaggerated cytokine expression, there were differences in immune cell populations and cell-type specific responses. These interesting findings indicate that fetal exposure to inflammatory stimuli, even without fetal infection, results in changes in the neonatal immune cell phenotype and function leading to heightened immune activation. The results of this study differ from a trend towards a muted pro-inflammatory response seen in pediatric COVID-19, which is attributed to cause decreased disease severity. The mechanisms underlying neonatal immune programming, the timing and severity of maternal exposure in relationship to immune programming and long-term health consequences need to be explored in future studies.