518. Newborn immune transcriptome changes rapidly and is shaped by maternal SARS-CoV-2 infection and/or vaccination
Authors: Xu Zhaohui , Sanchez Pablo J , Cohen Shira H , Pérez Latorre Leire , Pifer Traci , Rijal Manish , Mertz Sara , DeAntonio Rodrigo , Rood Kara , Abdelwahab Mahmoud , Reyes Osvaldo , Bartholomew Anna , Saez Llorens Xavier , Costantine Maged M , Mejias Asuncion , Ramilo Octavio 
Published: January 2025

Abstract

Background
SARS-CoV-2 infection during pregnancy is associated with adverse maternal effects, but its impact on infant’s immune development is not well defined. Using transcriptional profiles we analyzed the impact of SARS-CoV2 infection and/or vaccination in pregnant people and their infants longitudinally
Transcriptome changes in pregnant people with SARS-CoV-2 infection and/or vaccination
Modular analysis of pregnant people with SARS-CoV-2 infection and/or vaccination compared with healthy uninfected controls. Red dot: overexpression, blue dot: underexpression, white/empty space no difference vs controls

Methods
Multicenter observational study of SARS-CoV-2-infected and/or vaccinated pregnant people and their infants. Pregnant people (infected [n=91], vaccinated [n=42], infected-and-vaccinated [n=14], controls [n=22]) and their infants (n=81, 38,14, 11, respectively) were included. Maternal blood samples were collected during different trimesters and at delivery. Infant blood samples were collected longitudinally from birth (&lt; 72 hours), at 1 week and 1, 3 and 6 months of age. Whole blood RNA was extracted for RNA-sequencing and transcriptomic data analyzed with R
Transcriptional analysis of immune system development in early life
Modular gene expression scores were analyzed longitudinally of individual infant samples. Red: higher expression, white: lower expression. D1-3: days 1 to 3, W1: week 1, M1: month 1, M3: month 3, M6: month 6

Results
Compared with uninfected controls, interferon and plasma cells genes were overexpressed in pregnant people with acute infection (&lt; 14 days), but underexpressed with earlier infection or vaccination during pregnancy (Figure 1). Newborns &lt; 72 h of age (from all groups) showed significantly increased expression of erythrocytes, neutrophils, and inflammation genes. Expression of T/cytotoxic cell genes started to be observed at 1 week, while expression of B cells, plasma cells and interferon genes was observed at 3 months of age (Figure 2). Quantitative gene set enrichment analysis showed that compared to controls, infants from infected and/or vaccinated mothers had increased expression of interferon, while neutrophil, and adaptive immunity genes were decreased (Figure 3)
SARS-CoV-2 infection and/or vaccination of pregnant people shaped immune profiles of their infants
Fold changes of gene sets in infants compared to controls are shown (adjusted p-value &lt;0.01) from quantitative gene set enrichment (QuSAGE) analysis. Red: overexpression, blue: underexpression. Infant groups are defined by maternal infection and/or vaccination status at delivery.

Conclusion
Interferon and plasma cells related pathways were overexpressed in pregnant people with acute COVID-19, while vaccination and SARS-CoV-2 infection earlier in pregnancy were associated with under-expression of both innate and adaptive immunity genes. The infant immune system changed rapidly in the first few days of life, as different immune programs followed separate time trajectories. Maternal SARS-CoV-2 infection and/or vaccination shaped the immune profiles of their newborns, suggesting a potential impact on their immune development

Disclosures
Rodrigo DeAntonio, MD, MSc, DrPH, GSK: Grant/Research Support|Moderna: Grant/Research Support|Sanofi: Grant/Research Support Asuncion Mejias, MD, PhD, MsCS, Astra-Zeneca: Advisor/Consultant|Astra-Zeneca: Honoraria|Enanta: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi-Pasteur: Advisor/Consultant|Sanofi-Pasteur: Honoraria Octavio Ramilo, MD, Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Advisor/Consultant|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Grant/Research Support|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Honoraria|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): SAC member for MSD