Cerebrospinal fluid (CSF) and peripheral markers of the neuropsychiatric sequelae of COVID-19: The Generation C-SF pregnancy study

Summary The placenta is an integral organ during pregnancy, being a regulator of the in-utero environment including maternal neuroendocrine changes. Previous efforts have begun to elucidate a connection between HPA-axis gene expression in the placenta and maternal mental health, implicating that dysregulation of gene expression in the placenta has potential consequences for both the physical and mental health of the pregnant individual. Fully interrogating this connection is imperative, and there is an urgent need to expand our understanding of the role placental gene expression plays. This is especially important in the context of the coronavirus disease 2019 (covid-19) pandemic, as infections and the inflammatory responses they elicit have the potential to have a negative effect on maternal mental health. The parent study (Generation-CSF) is currently using a large ongoing pregnancy cohort to investigate the impact of SARS-CoV-2 infection and subsequent inflammatory changes on maternal mental health and cognition through paired blood and CSF (Cerebrospinal fluid) samples and psychiatric and cognitive assessments during and after pregnancy. This supplement aims to expand upon this investigation by clarifying the role that the placenta, as a regulator of neuroendocrine chances, could be playing in this relationship. By utilizing already collected placental samples and existing RNAseq data to investigate immune and inflammation genes in the placenta, which have yet to be explored in connection to maternal mental health, this supplement provides important additional information about what could be driving the proposed negative system wide changes that occur after infection during pregnancy. We hypothesize that SARS-CoV-2 infection during pregnancy will be positively associated with the expression of immune and inflammation markers in the placenta and maternal blood and that this upregulation will serve as a driver for increased EPDS scores at birth and at 6 weeks postpartum. In Aim 1 we will examine the association between SARS-CoV-2 infection and the expression of a curated list of 497 immune and inflammation related genes in the placenta with EPDS scores at birth and 6 weeks postpartum. In Aim 2 we will examine the association between cytokine levels in the blood (Il-1b, Il-17A, Il-6, CRP) and placental genes linked to SARS-CoV-2 and postpartum depression (EPDS scores) at birth and at 6 weeks postpartum. Finally, in Aim 3 we will validate key findings/candidate genes from Aim 1 and 2 in placental samples using quantitative gene expression profiling (qPCR).