The dialog between mother and newborn: insights from immune mediator crosstalk elicited by antenatal SARS-COV-2 exposure

Abstract

Goal: The present study intended to evaluate whether the profile of soluble immune mediators observed in cord blood samples resembles the pattern identified for mother serum samples.

Methods: For this purpose, parallel analysis of chemokines, cytokines, and growth factors was carried out in mother-newborn paired samples from acute and convalescent COVID-19 subgroups (Early, Intermediate, and Late) as well as healthy controls (HC).

Results: Data demonstrated that increased levels of CCL11, IFN-γ, IL1-Ra, and G-CSF were observed in cord blood samples from most COVID-19 subgroups, with fold change magnitude from 1.6× to 8.2× as compared with HC. Comparative analysis of mother-newborn pairs demonstrated that several immune mediators (CCL11, CCL4, IFN-γ, PDFG, and G-CSF) exhibited high increment magnitude in cord blood as compared with mother serum, reaching values up to 15.7×, mainly at convalescent COVID-19 infection. The signatures of soluble immune mediators revealed distinct waveforms for cord blood and mother serum, with a waning of immune mediators in the latter, contrasting with the increasing set of molecules in the former from acute toward convalescent COVID-19. Integrative network analysis of immune mediators in mother-newborn pairs showed an increase of neighborhood connectivity both in microenvironments and in their interplay from acute toward late convalescent COVID-19. Our results support the hypothesis of the interplay between mother serum and cord blood microenvironment that may impact the fetus development.

Conclusion: Together, this evidence regarding the maternal-fetal crosstalk can ultimately subsidize the improvement of clinical practice and public health policies for management of prenatal exposure to SARS-CoV-2 infection.

Keywords: COVID-19; immunological mediators; maternal serum; maternal-fetal communication; prenatal exposure; umbilical cord blood.