Mediators of inflammation at the maternal-fetal interface are altered by SARS-CoV-2 infection and pandemic stress

Problem: It is now recognized that SARS-CoV-2 infection and pandemic-related stress impacts maternal health. However, their effects at the maternal-fetal interface are still debated. Method of study: We recruited 199 women between March 2020 and July 2021, 79 SARS-CoV-2+ and 120 negative (the latter exposed to pandemic stress only). We also included 40 historic controls (i.e. pre-pandemic uncomplicated pregnancies recruited before March 2020). Placental samples were collected for protein and histological analysis. Results: The majority of SARS-CoV-2+ women were multiethnic, had higher pre-pregnancy BMI and elevated preterm birth rate (17%) vs SARS-CoV-2– or historic control. Placental inflammatory profile revealed increased IL-1Ra and CRP, independently of SARS-CoV-2 status, whilst MCP-1, IL-6 and IFNγ were elevated in the negative, but pandemic stress-exposed, group. These changes were predominant in placentas with inflammatory lesions on histopathological analysis. Furthermore, we observed elevated immune cells (CD45+) in placentas from SARS-CoV-2+ and negative pregnancies vs historic controls, even when individuals with pregnancy complications were excluded. Conclusions: Placental inflammatory profiles differed between SARS-CoV-2 statuses, namely exposed to pandemic stress +/- SARS-CoV-2 infection. This highlights the need to understand the differences between the effects of pandemic-related stress and the added burden of SARS-CoV-2 infection on placental health.