The placental transcriptomic profile determined by maternal COVID-19 disease encompasses alterations reminiscent of preeclampsia

During initial stages of the pandemic, SARS-CoV-2 infection during pregnancy was related to adverse pregnancy outcomes and alterations in the placenta. Whether placental abnormalities in pregnant women with COVID-19 still persist afterwards remains poorly studied. Here, we determined whether the absence of obstetric complications after maternal COVID-19 disease, including preeclampsia, is accompanied by a complete return to normalcy in terms of placental physiology.

Placental RNA was purified from placental samples from SARS-CoV-2 positive mothers taken either in 2022, when Omicron was the predominant variant of concern (termed Omicron) (n = 21); or from healthy pregnancies predating the pandemic (termed preCOVID-19). Our cohort included samples from pregnant women who got infected weeks and even months before term. We performed RNA-seq, identified differentially expressed genes and examined to which biological, biochemical and cellular pathways they belong, using gene set enrichment analysis.

We identified 71 differentially expressed genes (DEGs) (defined by p-value ≤0.05 and fold change (FC) of ≤ -2 or ≥2). The alterations identified in placentas delivered by mothers who suffered an episode of COVID-19 disease could be mainly attributed to pathways related to organogenesis, extracellular matrix organization and oxygen transport. These alterations were also detected after exclusion of gestational diabetes mellitus (GDM) samples. Although none of the samples were taken from cases of preeclampsia, several of the relevant DEGs have been previously reported as dysregulated in hypertensive disorders of pregnancy including preeclampsia.

We propose that maternal SARS-CoV-2 infection causes alterations in gene expression that are indicative of vascular defects in the placenta.