625 - Significance of placental SARS-CoV-2 viral replication in mothers with COVID-19 disease

The impact of SARS-CoV-2 infection during pregnancy on the placenta and the newborn remains poorly understood. Several reports demonstrate increased morbidities in preterm infants born to COVID-positive mothers, although they tested negative for SARS-COV-2. Several studies have shown the detection of SARS-COV-2 positive-sense RNA in the placenta, indicating the presence of the virus, but few studies have investigated the detection of live replicating SARS-COV-2 virus in the placenta. In this study, we investigated the relationship between maternal COVID disease and the placental expression of SERPINE1. SERPINE1 codifies the Plasminogen Activator Inhibitor (PAI-1), a protein that plays an important role in inhibiting fibrinolysis. miR-30c-5p is a known down regulator of this protein. Upregulation of SERPINE1 is linked to increased thrombosis, recurrent implantation failure, and preeclampsia.

Objective:

To investigate the association between active SARS-CoV-2 viral replication in placentas from preterm deliveries after maternal COVID disease and placental expression of SERPINE1.

Design/Methods:

SARS-CoV-2 positive placentas from preterm delivery < 32 weeks gestation were identified by Real-time PCR and immunohistochemistry (IHC). In-Situ Hybridization for SARS-COV-2 orf1ab negative-strand was done to determine the replication status of the virus. SERPINE1 gene expression was performed by ddPCR, and the miRNA 30c-5p expression was determined by PCR. IHC identified the localization of PAI-1 in the placental tissues.

Results:

We performed ddPCR expression analysis of SERPINE1 in placentas from 4 different groups based on SARS-CoV-2 detection: Group 1: no maternal COVID disease (n = 11); Group 2, maternal COVID disease, but no placental SARS-CoV-2 infection (n = 4); Group 3, maternal COVID disease and placental SARS-CoV-2 infection but no viral replication (n = 3); Group 4, maternal COVID disease,  placental SARS-CoV-2 infection and viral replication (n = 4). Two placental samples in Group 4 belong to neonates with SARS-CoV-2 vertical transmission. Placentas with active viral replication (Group 4) was associated with a significant increase in SERPINE1 expression (Figure 1) as well as dysregulation of miR-30c-5p placental levels. IHC showed intense PAI-1 staining throughout the placental tissues in group 4 compared to other groups.

Conclusion(s):

Placental transcriptomic responses to maternal COVID disease appear to be modified by active SARS-CoV-2 viral replication. Placental evaluation for SARS-CoV-2 infection after maternal COVID disease should include testing for live and replicating SARS-CoV-2 virus.