Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection.

Background and objective: COVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy. Methods: Expression of IFN activation signaling pathway molecules, including cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNß were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review. Results: Except BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells. Conclusions: STING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection

Background and objective COVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy. Methods Expression of IFN activation signaling pathway molecules, including cyclic GMP–AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNβ were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review. Results Except BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells;IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs);and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells. Conclusions STING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

Highly socially vulnerable communities exhibit disproportionately increased viral loads as measured in community wastewater.

Wastewater surveillance has proven to be a useful tool for evidence-based epidemiology in the fight against the SARS-CoV-2 virus. It is particularly useful at the population level where acquisition of individual test samples may be time or cost-prohibitive. Wastewater surveillance for SARS-CoV-2 has typically been performed at wastewater treatment plants; however, this study was designed to sample on a local level to monitor the spread of the virus among three communities with distinct social vulnerability indices in Shreveport, Louisiana, located in a socially vulnerable region of the United States. Twice-monthly grab samples were collected from September 30, 2020, to March 23, 2021, during the Beta wave of the pandemic. The goals of the study were to examine whether: 1) concentrations of SARS-CoV-2 RNA in wastewater varied with social vulnerability indices and, 2) the time lag of spikes differed during wastewater monitoring in the distinct communities. The size of the population contributing to each sample was assessed via the quantification of the pepper mild mottle virus (PMMoV), which was significantly higher in the less socially vulnerable community. We found that the communities with higher social vulnerability exhibited greater viral loads as assessed by wastewater when normalized with PMMoV (Kruskal-Wallis, p < 0.05). The timing of the spread of the virus through the three communities appeared to be similar. These results suggest that interconnected communities within a municipality experienced the spread of the SARS-CoV-2 virus at similar times, but areas of high social vulnerability experienced more intense wastewater viral loads.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.