Impact of Gestational Maternal SARS-CoV-2 Infection on Neonatal Inflammatory Biomarkers

Since the beginning of the pandemic, millions of pregnant women have been exposed to SARS-CoV-2, raising concerns about maternal and fetal sequelae. Yet, the impact of SARS-CoV-2 on the child's immune response remains largely unexplored. Herein, we leverage 833 mother-infant dyads from a New York City-based pregnancy cohort, to explore prospective associations between maternal gestational SARS-CoV-2 infection and inflammatory biomarkers in newborns. Of the mothers, 100 were infected with SARS-CoV-2 during pregnancy, as confirmed through self-report, antibody and/or PCR test results. We obtained 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 at birth. We also conducted stratified analyses by timing of infection in early (<20 weeks) versus late (≥20 weeks) gestation.

Higher levels of 22 inflammatory biomarkers (p _adj <0.05), including CD5, TNFSF14, CD8a, TGF-α, and CD244, were observed in neonates prenatally exposed to SARS-CoV-2 compared to unexposed neonates (p _adj <0.05). Early-gestation infection was associated with increased levels of eight inflammatory biomarker, including TNSF14, TGF-α, EN-RAGE, and decreased IL-18 levels, while late-gestation infection was linked to elevations in 12 biomarkers, including CD5, CD6, PD-L1.

Our results indicate that maternal SARS-CoV-2 infection during pregnancy impacts inflammatory biomarkers in newborns, with the timing of infection playing a critical role in shaping these immune profiles. Thus, this study underscores the need for further research and long-term follow-up to assess any potential future health consequences for the child.