Towards an understanding of COVID-19-associated preeclampsia.

INTRODUCTION

SARS-CoV-2 infection during pregnancy has been associated with higher rates of preeclampsia (PE). While placental abnormalities resembling PE have been reported in COVID-19 pregnancies, the molecular mechanisms underlying the association remain unclear.

METHODS

We conducted bulk RNA sequencing on placental tissues from four pregnancy groups: uneventful prepandemic (preCOVID-19), prepandemic PE (preCOVID-19 PE), COVID-19 without PE (COVID no PE), and COVID-19 complicated by PE or other hypertensive disorders (COVID PE). Differential expression was analyzed using Deseq2 likelihood ratio test (LRT), and gene set enrichment analysis identified dysregulated pathways.

RESULTS

Clustering of LRT-significant differentially expressed genes (DEGs) identified a set of 16 genes (defined by the false discovery rate adjusted p-value < 0.05) across the four pregnancy groups, showing stepwise expression changes-lowest in preCOVID-19 uneventful, followed by those in COVID-19 without PE, then preCOVID-19 PE, and highest in COVID PE. This cluster included genes associated with placental dysfunction, such as LAMA5 and BTNL9. While morphogenesis-related pathways were enriched across all pathological groups, immune activation pathways were predominantly enriched in COVID PE, moderately in preCOVID-19 PE, and absent in COVID no PE.

DISCUSSION: Our findings identify a COVID-19-associated placental signature that mirrors PE features and shows a progressive expression pattern defining a continuum of placental stress, with maternal SARS-CoV-2 infection potentially exacerbating underlying dysfunction.