COVID-19 in pregnancy: implications for fetal brain development

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has been rarely observed in SARS-CoV-2 to date, given the potential for profound maternal immune activation (MIA), impact on the developing fetal brain is likely. Here we review evidence that SARS-CoV-2 and other viral infections during pregnancy can result in maternal, placental, and fetal immune activation, and ultimately in offspring neurodevelopmental morbidity. Finally, we highlight the need for cellular models of fetal brain development to better understand potential short- and long-term impacts of maternal SARS-CoV-2 infection on the next generation. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is known to confer a risk of increased morbidity and mortality for the mother, but data are lacking regarding the impact of maternal SARS-CoV-2 infection on the developing fetal brain.Placental and fetal infection with SARS-CoV-2 have been rare to date; SARS-CoV-2 infection in pregnancy appears most likely to impact fetal brain development via maternal and placental immune activation.Maternal, placental, and fetal immune activation have been observed in SARS-CoV-2 infection during pregnancy, and adverse neurodevelopmental outcomes have been reported in early follow-up studies of offspring.Maternal and placental immune activation may impact the placenta and developing fetal brain via induction of immune activation and proinflammatory cytokine production, dysregulation of serotonin/other neurotransmitter signaling, and increased oxidative stress.