The potential impact of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the developing fetal brain is not yet understood. Other maternal infections, including viral infections such as influenza, have consistently been associated with adverse neurodevelopmental outcomes in offspring, including autism, schizophrenia, cerebral palsy, cognitive dysfunction, bipolar disorder, anxiety and depression. As SARS-CoV-2 can stimulate immune activation that is, if anything, more substantial than other risk-associated infections, it is likely that the developing fetal brain may be similarly impacted by SARS-CoV-2-induced maternal immune activation (MIA) during key developmental windows.
Using a murine model of MIA, Jun Huh and colleagues previously demonstrated that maternal T helper 17 (TH17) cells1 and maternal gut bacteria inducing TH17 cell differentiation2 promote neurodevelopmental abnormalities in male but not female offspring3. These studies were funded in part by a SFARI Research Award.
Based on these findings, and their recent work that demonstrates maternal SARS-CoV-2 infection in pregnancy is associated with an increased risk for offspring neurodevelopmental disagnosis at one year of age4,5, Andrea Edlow and collaborators hypothesize that SARS-CoV-2 infection in pregnancy will induce changes in maternal immune cell function and gut microbiota composition; these changes will act synergistically to increase IL-17a in the maternal circulation. Maternal IL-17a responses will in turn induce sex-specific immunological changes in placenta and cord blood cells, which will correlate with sex-biased adverse neurodevelopmental outcomes in offspring. To investigate this, the researchers aim to extensively characterize SARS-CoV-2-induced immune responses in both pregnant women and fetuses.
To achieve this aim, the research team has initiated the collection of samples from more than 400 maternal participants, including maternal and cord blood plasma, sera, peripheral blood mononuclear cells (PMBCs), maternal stool specimens, rectal swabs, placental biopsies and breast milk, among other samples. The supplemental funding from SFARI will be instrumental in enabling additional samples to be collected from participants as well as expediting the processing of samples. It will also help to increase capacity for family tracking and retention activities that will be critical for correlating maternal-placental-fetal biology with outcomes in early childhood.
Successful outcomes of the proposed work will serve as a foundation for future endeavors to understand how maternal coronavirus disease 2019 (COVID-19) infection produces long-term neurodevelopmental effects on children through maternal and fetal immune responses.