NLRP3 inflammasome activation in the placenta during SARS-CoV-2 infection

The NLRP3 inflammasome is a key regulator of innate immunity. Its overactivation contributes to cytokine release and tissue inflammation during SARS-CoV-2 infection. However, its role in placental inflammation and pregnancy outcomes remains unclear.

To evaluate whether SARS-CoV-2 infection during pregnancy induces NLRP3 inflammasome activation in placental tissue and to assess its association with maternal and neonatal outcomes.

A prospective cohort study included 25 pregnant women with RT-PCR-confirmed COVID-19 and 25 healthy controls. Placental NLRP3, Caspase-1, IL-1β, and IL-18 expression were analyzed by qRT-PCR and Western blotting. Maternal and cord plasma cytokines were quantified by ELISA and cytometric bead array. Viral RNA, antibody transfer, and nutrient transporter gene expression were also evaluated.

Placentas from infected women showed higher NLRP3 (p = 0.015) and Caspase-1 (p = 0.029) mRNA levels compared with controls. Western blotting detected procaspase-1 (∼50 kDa) and cleaved caspase-1 (∼35 kDa), indicating inflammasome activation. Maternal IL-18 concentrations were elevated (p = 0.013), while IL-1β remained unchanged. SARS-CoV-2 RNA was identified in 8 % of placentas (variants 21H and 20A). IgG antibodies were found in 28 % of maternal and 24 % of cord samples (p = 0.017). Infected pregnancies showed lower gestational age at delivery (p = 0.023), higher cesarean rate (p = 0.004), and lower neonatal Apgar scores (p = 0.006, p = 0.015). Nutrient transporter expression was preserved.

SARS-CoV-2 infection during pregnancy induces activation of the NLRP3 inflammasome in placental tissue and systemic elevation of IL-18, indicating both local and systemic inflammation.