Prenatal exposure to maternal SARS-CoV-2 infection leads to altered neuro-immune biomarker profiles at birth.

Maternal infection during pregnancy can induce immune-mediated biological adaptations that influence fetal neurodevelopment. Although vertical transmission of SARS-CoV-2 is uncommon, the impact of maternal infection on fetal neuroimmune signaling remains poorly characterized. We investigated whether prenatal exposure to maternal SARS-CoV-2 infection is associated with alterations in circulating neuroimmune biomarkers detectable at birth. In this case-control study, 28 women with SARS-CoV-2 infection during pregnancy and 61 uninfected controls were enrolled. Maternal and cord blood samples were collected at delivery. Following an initial inflammatory screening, neuro-specific biomarkers (NfL, Tau, P-Tau217, GFAP, S100β, α-Synuclein) and PTX3 were measured. Correlation network analyses, PTX3 promoter methylation assessment, and haplotype stratification analyses were also performed. Systemic inflammatory mediators did not differ significantly between groups. In contrast, neonates exposed to maternal SARS-CoV-2 infection exhibited significantly lower cord blood concentrations of GFAP, NfL, and P-Tau217 and increased α-Synuclein levels compared with controls. Tau showed a decreasing trend, whereas S100β and PTX3 remained unchanged. Network analyses revealed reduced cytokine connectivity but enhanced interactions among neuro-specific biomarkers. Although PTX3 promoter methylation was unchanged, the PTX3 h2/h2 haplotype appeared to modulate biomarker interaction patterns. To our knowledge, this is the first study to characterize a circulating neuro-specific biomarker signature in neonates prenatally exposed to maternal SARS-CoV-2 infection. This supports the utility of neuroimmune biomarker networks as translational tools to investigate the biological consequences of maternal immune activation during pregnancy.