Placental immune response to SARS-CoV-2 infection: Analysis of pyroptosis and interleukin-6 signaling

Coronavirus Disease 2019 (COVID-19) has caused millions of infections and deaths globally, with pregnant women being a particularly vulnerable population. Pregnant women infected with COVID-19, along with their fetuses and neonates, experience increased morbidity and mortality. The angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors, which are expressed in both lung epithelial cells and the placenta, facilitate viral entry and contribute to pyroptosis and excessive inflammation. Therefore, investigating the placental inflammatory response, specifically through the role of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomers and interleukin-6 (IL-6) antibodies, is crucial to understanding the impact of COVID-19 on pregnancy outcomes. This cross-sectional study examined placental inflammation in 64 third-trimester pregnancies. Placental paraffin blocks were divided into two groups: those from women infected with COVID-19 (n=32) and those from uninfected women (n=32). Immunohistochemistry was used to assess the expression of ASC oligomers and IL-6 in the villous placental area.  ASC oligomer expression was significantly higher in the COVID-19 group (p=0.001), while no difference was observed for IL-6 expression. Furthermore, subgroup analysis based on COVID-19 symptom severity revealed no significant differences in the expression of ASC oligomers or IL-6 (p 0.05), and no correlation was found between ASC oligomer and IL-6 expression, while pyroptosis is more pronounced in the placentas of pregnant women infected with COVID-19, this heightened inflammatory response is not consistently associated with increased pro-inflammatory cytokine production. Furthermore, COVID-19 severity did not appear to influence the degree of placental pyroptosis.