SARS-CoV-2 infection during
pregnancy leads to an increased
risk of adverse
pregnancy outcomes. Although the
placenta itself can be a target of
virus infection, most
neonates are
virus free and are born healthy or recover quickly. Here, we investigated the impact of SARS-CoV-2 infection on the
placenta from a cohort of
women who were infected late during
pregnancy and had tested nasal swab positive for
SARS-CoV-2 by qRT-
PCR at delivery.
SARS-CoV-2 genomic and subgenomic
RNA was detected in 23 out of 54
placentas. Two
placentas with high
virus content were obtained from
mothers who presented with severe COVID-19 and whose
pregnancies resulted in adverse outcomes for the
fetuses, including intrauterine
fetal demise and a preterm delivered baby still in
newborn intensive care. Examination of the placental samples with high
virus content showed efficient SARS-CoV-2 infection, using
RNA in situ hybridization to detect genomic and replicating
viral RNA, and
immunohistochemistry to detect
SARS-CoV-2 nucleocapsid protein.
Infection was restricted to
syncytiotrophoblast cells that envelope the fetal
chorionic villi and are in direct contact with maternal
blood. The infected
placentas displayed massive infiltration of maternal immune
cells including
macrophages into intervillous spaces, potentially contributing to
inflammation of the
tissue. Ex vivo
infection of placental
cultures with
SARS-CoV-2 or with
SARS-CoV-2 spike (S)
protein pseudotyped
lentivirus targeted mostly
syncytiotrophoblast and in rare events
endothelial cells.
Infection was reduced by using
blocking antibodies against ACE2 and against
Neuropilin 1, suggesting that
SARS-CoV-2 may utilize alternative receptors for entry into placental
cells.