SARS-CoV-2 (COVID-19) as a possible risk factor for neurodevelopmental disorders

Abstract

Pregnant women constitute one of the most vulnerable populations to be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019. SARS-CoV-2 infection during pregnancy could negatively impact fetal brain development via multiple mechanisms. Accumulating evidence indicates that mother to fetus transmission of SARS-CoV-2 does occur, albeit rarely. When it does occur, there is a potential for neuroinvasion via immune cells, retrograde axonal transport, and olfactory bulb and lymphatic pathways. In the absence of maternal to fetal transmission, there is still the potential for negative neurodevelopmental outcomes as a consequence of disrupted placental development and function leading to preeclampsia, preterm birth, and intrauterine growth restriction. In addition, maternal immune activation may lead to hypomyelination, microglial activation, white matter damage, and reduced neurogenesis in the developing fetus. Moreover, maternal immune activation can disrupt the maternal or fetal hypothalamic-pituitary-adrenal (HPA) axis leading to altered neurodevelopment. Finally, pro-inflammatory cytokines can potentially alter epigenetic processes within the developing brain. In this review, we address each of these potential mechanisms. We propose that SARS-CoV-2 could lead to neurodevelopmental disorders in a subset of pregnant women and that long-term studies are warranted.