Integrative Analysis of Cytokines, miRNAs, and Serotonin in Umbilical Cord Blood and Their Association with Neurodevelopment after Gestational Exposure to COVID-19

• Grant number: 25/12948-6
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Helena Paula Brentani
• Grantee: Helena Paula Brentani
• Principal researcher abroad: Jaime Agustín Gutiérrez Pérez
• Institution abroad: Universidad San Sebastián, Chile
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Gisele Rodrigues Gouveia
• Associated research grant: 22/11795-3 - Impact of COVID-19 during pregnancy on infant neurodevelopment, AP.R

Abstract

SARS-CoV-2 infection during pregnancy has been associated with adverse neonatal outcomes, including preterm birth, intrauterine growth restriction, and increased risk of neurodevelopmental disorders. Recent evidence suggests that maternal immune activation and the excessive release of proinflammatory cytokines-referred to as a "cytokine storm"-may play a central role in this process, particularly by affecting the intrauterine environment and fetal brain development. However, the molecular mechanisms linking gestational inflammation to neurodevelopmental outcomes remain poorly understood, especially in the context of COVID-19.Our research group at the Faculty of Medicine of the University of São Paulo (FMUSP), supported by FAPESP (Grant 2022/11795-3), has been conducting a study on the molecular effects of gestational COVID-19 using umbilical cord blood, with a focus on identifying miRNA profiles associated with early neurodevelopmental outcomes. This Sprint proposal aims to complement and expand this ongoing study through an international collaboration with Universidad San Sebastián (USS), in Chile, by combining complementary expertise: while the Brazilian team has extensive experience in cytokine and miRNA analysis and neurodevelopment, the Chilean team is recognized for their work on protocols for the isolation and characterization of extracellular vesicles (EVs) in accordance with the International Society for Extracellular Vesicles, and is currently building expertise in neurotransmitter quantification in EVs.The objective of this proposal is to perform an integrated analysis of cytokines, miRNAs, and serotonin (EVs-associated) in umbilical cord blood samples from newborns exposed and unexposed to COVID-19 during pregnancy, and to evaluate their association with clinical neurodevelopmental outcomes. The planned activities include technical and scientific exchange missions between the two institutions, enabling the standardization of EV isolation and serotonin quantification protocols, scientific workshops, integrated data analyses, dissemination of findings, and the joint development of future collaborative projects.In the first year, a researcher from the FMUSP team will travel to the USS to conduct experiments and present the Brazilian group's research progress. In the second year, a researcher from USS will visit Brazil to participate in the integrated data analysis and plan the next stages of the research. As outcomes, the collaboration is expected to result in the submission of at least one joint scientific publication and the development of a new binational project to be submitted to funding agencies in both countries (e.g., FAPESP and ANID).This proposal not only strengthens a strategic international collaboration but also advances scientific knowledge on the impact of gestational COVID-19 on fetal programming, contributing to the identification of early biological markers of risk for altered neurodevelopment. The project also fosters the training of young researchers, the internationalization of Brazilian science, and the consolidation of long-term scientific partnerships. (AU)