Pregnant individuals with uncomplicated pregnancies display pro-inflammatory immune changes when exposed to the COVID-19 pandemic

Problem: The COVID-19 pandemic has been shown to have a detrimental impact on the mental health of pregnant individuals, and chronic stress can alter the immune profile. However, the effects of the COVID-19 pandemic on the immune system in pregnancy are still poorly understood. We aimed to evaluate the impact of pandemic exposure on the maternal immune profile in uncomplicated pregnancies. Method of study: We collected blood and placenta samples from pregnant individuals exposed and unexposed to the pandemic to compare their immune and inflammatory profiles. We performed co-culture with circulating maternal immune cells and endothelial cells to assess endothelial activation. Statistical analysis was performed using unpaired t-test, Mann-Whitney, or Fisher's exact test as appropriate. Results: In exposed individuals, we observed a decreased proportion of Th2 cells (p <.0001) and Treg/Th17 ratio (p <.05), as well as an increased Th1/Th2 ratio (p <.0001). Levels of IL-1β (p <.01) and IL-18 (p <.01) were increased in the circulation of exposed participants, whilst other mediators were significantly decreased (IFNγ, IL-8, MCP-1, amongst others). Furthermore, we observed increased production of ICAM, hallmark of endothelial activation, when we co-cultured endothelial cells with immune cells from exposed individuals. Vaccination status impacted the cellular profile with increased proportions of Th1 and B cells in vaccinated participants. Conclusion: Overall, we observed a pro-inflammatory bias in the circulation of pregnant individuals exposed to the COVID-19 pandemic, with otherwise uncomplicated pregnancies. Our work also supports an association between the increased risk of endothelial activation/hypertension and SARS-CoV2 infection, which might be driven in part by exposure to the pandemic and associated stressors.