While pregnancy increases the risk for severe COVID19, the clinical and immunological implications of COVID19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID19 show increased inflammation and unique IFNλ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, ESM1, and reducing BGN and CD209. Finally, COVID19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3 and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.
Background
There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes.
Methods
This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment.
Results
Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16–33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities.
Conclusions
Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.
There is limited data on amniocentesis as a diagnostic tool for congenital Zika syndrome. Here we report on a prospective cohort of 16 women with suspected Zika virus infection in a highly endemic area, and discusss the role of amniocentesis in the prenatal diagnosis of fetal Zika infection.
Graphical abstract SummaryMaternal and/or fetal factors that influence Congenital Zika Syndrome (CZS) development remain elusive. Interferon lambda has been reported as an antiviral factor in Zika infections. Using functional analysis, we conducted a case-control study to demonstrate that maternal interferon lambda single nucleotide polymorphisms (SNPs) contribute to newborn protection. Mothers carrying CA/CC genotypes of rs8109886 SNP have 4.5 times reduced risk of having children with CZS. When we combined the genotypes CC from rs12979860 and CA/CC from rs8109886, 93% of the mothers delivered healthy newborns.Placenta coming from CZS cases displayed diminished level of IFNL2 along with higher tissue-specific type-I IFN genes, tagged by of IFIT5, indicating that lower IFNL levels upon ZIKV infection can lead to uncontrolled damage to overexpression of type-I IFN pathway.In summary, genetically regulated IFNL levels contribute to immune homeostasis and CZS prevention.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.