Abstract Background The COVID-19 pandemic has had a significant negative impact on the mental health of pregnant women with increased risk of perinatal anxiety and depression. Inflammatory processes play critical roles in psychiatric health and the placenta plays an integral role in modulating the maternal immune system throughout pregnancy. Aims 0.05) from the previous analysis (predictors) and log transformed EPDS scores around 6-weeks postpartum (continuous outcome) with linear regression adjusted for gestational age, Distressed Communities Index scores (DCI; a measure of economic wellbeing of communities) based on zip code, and pre-pregnancy BMI. A nominal p-value of 0.10 was used to establish genes of interest for further analysis. Study 2: In 167 additional placental samples, we generated gene expression data (qPCR) for the top 5 genes of interest from Study 1. We conducted differential gene expression analysis of these 5 genes by gestational SARS-CoV-2 status and then interrogated the relationship between these genes and log transformed postpartum EPDS scores with linear regression models adjusted for the same covariates as in Study 1. Finally, based on emerging literature of fetal sex as a key modulator of placental gene expression, we repeated these investigations in stratified analysis by fetal sex. Results In Study 1, prenatal SARS-CoV-2 infection was associated with downregulation of PTGER2 expression in the placenta, (logFC= -0.50, adjusted p-value =0.022) and dysregulation of 37 additional genes (unadjusted p-value 0.05). Placental expression of four (CXCR6, BANK1, KCNJ2, and MET) of these 38 SARS-CoV-2-associated genes was inversely associated with maternal postpartum EPDS scores (p-value 0.10). In Study 2, in the whole sample we could not find any significant association of SARS-CoV-2 infection with placental gene expression; nor an association of gene expression with postpartum EPDS scores. In fetal sex-stratified analyses, gestational SARS-CoV-2 infection was associated with lower CXCR6 expression in male placentas (ß= -0.87, p=0.03). There was an inverse association between female placental MET expression and postpartum EPDS scores (ß=-0.10, p=0.067). Discussion & Conclusions This study suggests that in placentas from individuals carrying male fetuses, gestational SARS-CoV-2 infection was associated with lower CXCR6 expression. Additionally, lower MET expression in the placentas from individuals carrying female fetuses may be associated with more severe postpartum depression symptoms at 6 weeks postpartum. However, this study does not fully validate either of these associations in two separate samples, and further research should be done to elucidate this potential connection.
Pérez-Rodríguez et al. (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: