Background: While risk of infection with SARS-CoV-2 is low to pregnant women and the fetus, there is increased risk of preterm birth and admission into ICU. The fetus is relatively protected against infection, with cases of vertical transmission being rare. Various receptors and accessory molecules which are known to regulate SARS-CoV-2 viral entry into host cells have soluble versions which could act as decoy traps. Following on from our previous findings regarding the abundance of some of these molecules in breast milk and amniotic fluid, we show the maternal-fetal interface is also rich in these molecules and how systemically they can be differentially expressed between males, non-pregnant females, pregnant females, and neonates. Methods: Archived placental samples from before the pandemic, and blood from participants in late 2020 who had not tested positive for COVID-19 were analysed for the presence of receptors by ELISA, immunohistochemistry, immunoblotting and flow cytometry. Results: We have confirmed that the placenta and membranes are particularly rich in CD26 and CD147 and gone on to consider if it is possible that shedding of these molecules into the maternal and fetal circulation occurs. However, except for sCD147 in umbilical cord plasma compared to all groups and sNRP-1 in pregnant women in comparison to men and neonates, the expression of soluble forms of these molecules is primarily consistent between the groups studied here. Conclusion: The maternal-fetal interface has potential mechanisms to protect the fetus from contracting SARS-CoV-2 by being rich with soluble versions of receptors involved in host cell entry of the virus, thereby limiting infection of host cells.

Healthy pregnancy is accompanied by various immunological and metabolic adaptations. Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia, and gestational diabetes mellitus (GDM), while posing a risk to the neonate. There is a lack of knowledge surrounding obesity and the maternal immune system. The objective of this study was to consider if immunological changes in pregnancy are sabotaged by maternal obesity. Peripheral blood was collected from fasted GDM-negative pregnant women at 26-28 weeks of gestation. Analysis was done using immunoassay, flow cytometry, bioenergetics analysis and cell culture. The plasma profile was significantly altered with increasing BMI, specifically leptin (r=0.7635), MCP-1 (r=0.3024) and IL-6 (r=0.4985). Circulating leukocyte populations were also affected with changes in the relative abundance of intermediate monocytes (r=-0.2394), CD4:CD8 T cell ratios (r=0.2789), and NKT cells (r=-0.2842). Monocytes analysed in more detail revealed elevated CCR2 expression and decreased mitochondrial content. However, LPS-stimulated cytokine production and bioenergetic profile of MNCs was not affected by maternal BMI. The Th profile skews towards Th17 with increasing BMI; Th2 (r=-0.3202) and Th9 (r=-0.3205) cells were diminished in maternal obesity, and CytoStimTM-stimulation exacerbates IL-6 (r=0.4166), IL-17A (r=0.2753), IL-17F (r=0.2973) and IL-22 (r=0.2257) production with BMI, while decreasing IL-4 (r=-0.2806). Maternal obesity during pregnancy creates an inflammatory microenvironment. Successful pregnancy requires Th2-biased responses yet increasing maternal BMI favours a Th17 response that could be detrimental to pregnancy. Further research should investigate key populations of cells identified here to further understand the immunological challenges that beset pregnant women with obesity.