A large proportion of pregnant women worldwide (21% in our CDC-funded Generation C cohort, current
n=2,545) has been recently exposed to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
and women of reproductive age continue to be infected despite widespread vaccination. However, the acute
and subacute effects of SARS-CoV-2 infection during the vulnerable period of pregnancy and postpartum are
not yet clear. Pregnancy and the postpartum are high-risk periods for coronavirus disease 19 (COVID-19) and
for developing neuropsychiatric symptoms. Infections and dysregulation of inflammatory processes in the
periphery and central nervous system (CNS) are thought to play a role in this vulnerability. We now know that
SARS-CoV-2 causes high rates of subacute and long-term psychiatric and cognitive sequelae in the general
population. There is a need to also understand the long-term effects of SARS-CoV-2 infection on mental health
and cognition in the vulnerable population of pregnant and postpartum women, especially because they often
are excluded from large cohort studies. We propose to study the long-term effects of prior SARS-CoV-2
infection on psychiatric and cognitive sequelae postpartum, with a mediating role of central and peripheral
inflammation. We will leverage a well-powered pregnancy cohort (Generation C cohort, target n>3,000)
established in April 2020 in New York, with 21% of the cohort previously exposed to SARS-CoV-2
infection to date. In a subset of this cohort (n=500), we propose to collect paired blood and cerebrospinal
fluid (CSF) samples, which will provide the unique opportunity to investigate the subacute and long-term
impacts of SARS-CoV-2 infection on inflammatory processes in the central nervous system (CNS). We
hypothesize that prior SARS-CoV-2 infection can lead to dysregulation of peripheral and central inflammatory
processes during pregnancy, and that this contributes to causing psychiatric symptoms and cognitive
dysfunction in the vulnerable post-partum period. Aim 1 will characterize the subacute and long-term impact of
prior exposure to SARS-CoV-2 on central and peripheral inflammation in pregnant women, including
measuring SARS-CoV-2 IgG antibodies, characterizing inflammatory profiles using a high-sensitivity multiplex
immunoassay for 11 inflammatory markers in CSF and blood, and examining the presence of neuronal
autoantibodies. Aim 2 will examine the association between prior SARS-CoV-2 exposure, central and
peripheral inflammation during pregnancy, and psychiatric symptoms postpartum. Aim 3 will examine the
association between prior SARS-CoV-2 exposure, central and peripheral inflammation during pregnancy, and
cognitive deficits in attention, memory and executive functioning postpartum.
