A Translational Perspective of Maternal Immune Activation by SARS-CoV-2 on the Potential Prenatal Origin of Neurodevelopmental Disorders: The Role of the Cholinergic Anti-inflammatory Pathway.

José Javier Reyes-Lagos,Juan Carlos Echeverría,Alejandra Vargas-Caraveo,Hugo Mendieta-Zerón,Gustavo Pacheco-López,Eric Alonso Abarca-Castro

doi:10.3389/fpsyg.2021.614451

Abstract

The emergent Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could produce a maternal immune activation (MIA) via the inflammatory response during gestation that may impair fetal neurodevelopment and lead to postnatal and adulthood mental illness and behavioral dysfunctions. However, so far, limited evidence exists regarding long-term physiological, immunological, and neurodevelopmental modifications produced by the SARS-CoV-2 in the human maternal-fetal binomial and, particularly, in the offspring. Relevant findings derived from epidemiological and preclinical models show that a MIA is indeed linked to an increased risk of neurodevelopmental disorders in the offspring. We hypothesize that a gestational infection triggered by SARS-CoV-2 increases the risks leading to neurodevelopmental disorders of the newborn, which can affect childhood and the long-term quality of life. In particular, disruption of either the maternal or the fetal cholinergic anti-inflammatory pathway (CAP) could cause or exacerbate the severity of COVID-19 in the maternal-fetal binomial. From a translational perspective, in this paper, we discuss the possible manifestation of a MIA by SARS-CoV-2 and the subsequent neurodevelopmental disorders considering the role of the fetal-maternal cytokine cross-talk and the CAP. Specifically, we highlight the urgent need of preclinical studies as well as multicenter and international databanks of maternal-fetal psychophysiological data obtained pre-, during, and post-infection by SARS-CoV-2 from pregnant women and their offspring.

Highlights

maternal immune activation (MIA) AND SARS-CoV-2During pregnancy, there is an increased risk of infection by viruses and bacteria (Silasi et al, 2015; Barinov et al, 2020)
Pregnancy was early considered as a highrisk condition for contracting the COVID-19 disease (Phoswa and Khaliq, 2020); approximately 200 million pregnant women were estimated as having a potential risk of SARS-CoV-2 infection worldwide (Vogel, 2020)
Recent evidence has shown that the occurrence of COVID-19 during gestation is mainly associated with higher preterm birth rates (Allotey et al, 2020)

Summary

Introduction

MIA AND SARS-CoV-2During pregnancy, there is an increased risk of infection by viruses and bacteria (Silasi et al, 2015; Barinov et al, 2020). Pregnancy was early considered as a highrisk condition for contracting the COVID-19 disease (Phoswa and Khaliq, 2020); approximately 200 million pregnant women were estimated as having a potential risk of SARS-CoV-2 infection worldwide (Vogel, 2020).

Results

Conclusion