Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies a preeclampsia-like gene signature

In recent years, pregnant people infected with the SARS-CoV-2 virus have shown a higher incidence of “preeclampsia-like syndrome”. Preeclampsia is a systematic syndrome that affects 5-8 % of pregnant people worldwide and is the leading cause of maternal mortality and morbidity. It is unclear what causes preeclampsia, and is characterised by placental dysfunction, leading to poor placental perfusion, maternal hypertension, proteinuria, thrombocytopenia, or neurological disturbances.In this study, we used whole-transcriptome, digital spatial profiling of placental tissues to analyse the expression of genes at the cellular level between placentae from pregnant participants who contracted SARS-CoV-2 in the third trimester of their pregnancy and those prior to the start of the pandemic. Our focused analysis of the trophoblast and villous core stromal cell populations revealed tissue-specific pathways enriched in the SARS-CoV-2 placentae that align with a pre-eclampsia signature. Most notably, we found enrichment of pathways involved in vascular tension, blood pressure, inflammation, and oxidative stress.This study illustrates how spatially resolved transcriptomic analysis of placental tissue can aid in understanding the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy that are thought to induce “preeclampsia-like syndrome”. Moreover, our study highlights the benefits of using digital spatial profiling to map the crosstalk between trophoblast and villous core stromal cells linked to pathways involved in “preeclampsia-like syndrome” presenting in pregnant people with SARS-CoV-2.