493 - Impact of Gestational Maternal SARS-Cov-2 Infection on Neonatal Inflammatory Biomarkers.

Publication Number: 3475.493

Bushra Amreen, Icahn School of Medicine at Mount Sinai, Astoria, NY, United States; Floriana Milazzo, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Darwin D’Souza, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Natalie Samper, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Seunghee Kim-schulze, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Whitney Lieb, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Frederieke Gigase, Erasmus, Rotterdam, Zuid-Holland, Netherlands; veerle bergink, Icahn School of Medicine at Mount Sinai, new york, NY, United States; Jia Chen, Ichan School of Medicine at Mount Sinai, New York, NY, United States; Corina Lesseur, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Anna-Sophie Rommel, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Background: Since the beginning of the pandemic, millions of pregnant women have been exposed to SARS-CoV-2, raising concerns about fetal sequelae. Yet the impact SARS-CoV-2 on the child's immune response remains largely unexplored.

Objective: To explore prospective associations between maternal gestational SARS-CoV-2 infection and inflammatory biomarkers in newborns.

Design/Methods: We leveraged 833 mother-infant dyads from a New York City-based pregnancy cohort, Generation C. Of the 833 mothers, 100 were infected with SARS-CoV-2 during pregnancy. We measured 92 inflammatory biomarker levels in neonatal dried blood spots (DBS) using the Olink® Target 96 Inflammation panel. Empirical Bayes method was used to fit linear regression models to assess the effects of maternal infection during pregnancy on neonatal inflammatory markers. We also conducted stratified analyses by timing of infection during pregnancy early ( < 20 weeks) vs late (≥20 weeks) gestation. All models were adjusted for maternal age, race, COVID-19 vaccination status, pre-pregnancy BMI, cardio-metabolic pregnancy complications, preterm birth, delivery mode, child sex and age at DBS collection.

Results: In the overall analysis, 22 inflammatory biomarkers including CD5, TNFSF14, CD8a, TGF-α, and CD244 were elevated in the exposed neonates compared to the unexposed (padj < 0.05). In the early gestation infection group, 8 inflammatory biomarkers including TNSF14, TGF-α, EN-RAGE were increased while IL-18 levels were decreased compared to the unexposed group. In the late gestation infection group, 12 biomarkers including CD5, CD6, PD-L1 were elevated compared to the unexposed group. (See Figure 1)

Conclusion(s): Our study is among the first to examine neonatal inflammatory markers in a large cohort of children with gestational exposure to SARS-CoV-2, and the first to evaluate how the timing of prenatal exposure affects inflammatory profiles at birth. The patterns observed indicate that prenatal exposure to SARS-CoV-2, during early gestation may prime neonates toward inflammatory and tissue-repair responses. In contrast, inflammation due to late exposure resemble that of active infection or post-infection hyper-inflammation in adults. Our results indicate that gestational SARS-CoV-2 infection impacts inflammatory biomarkers in newborns, and timing of infection plays a critical role in shaping these immune profiles, underscoring the need for further research and long-term follow-up to assess potential health consequences for the children.

Figure 1:
Volcano plots of differentially regulated inflammatory markers, in neonatal dried blood spots, using linear regression models adjusted for maternal age, race, vaccination status, pre-pregnancy BMI, preterm birth, delivery mode, infant sex, age at DBS collection and cardiometabolic pregnancy complications. A. Overall model of exposed group (n=100) compared to unexposed group (n=726). B. Model of early gestational exposure group (n=38) compared to unexposed group (n=726). C. Model of late infection group (n=62) compared to unexposed group (n=726).The x-axis is the log2 fold change (Log2FC) and y-axis is the -log10 P-value, the points highlighted in blue and maroon are markers with padj < 0.05. Right quadrants of the vertical dashed line represent upregulation of markers while left quadrants represent down regulation.