Association between Viral Infections and Risk of Autistic Disorder: An Overview

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition of the central nervous system (CNS) that presents with severe communication problems, impairment of social interactions, and stereotypic behaviours. Emerging studies indicate possible associations between viral infections and neurodegenerative and neurobehavioural conditions including autism. Viral infection during critical periods of early in utero neurodevelopment may lead to increased risk of autism in the offspring. This review is aimed at highlighting the association between viral infections, including viruses similar to COVID-19, and the aetiology of autism. A literature search was conducted using Pubmed, Ovid/Medline, and Google Scholar database. Relevant search terms included “rubella and autism”, “cytomegalovirus and autism”, “influenza virus and autism”, “Zika virus and autism”, “COVID-19 and autism”. Based on the search terms, a total of 141 articles were obtained and studies on infants or children with congenital or perinatal viral infection and autistic behaviour were evaluated. The possible mechanisms by which viral infections could lead to autism include direct teratogenic effects and indirect effects of inflammation or maternal immune activation on the developing brain. Brain imaging studies have shown that the ensuing immune response from these viral infections could lead to disruption of the development of brain regions and structures. Hence, long-term follow up is necessary for infants whose mothers report an inflammatory event due to viral infection at any time during pregnancy to monitor for signs of autism. Research into the role of viral infection in the development of ASD may be one avenue of improving ASD outcomes in the future. Early screening and diagnosis to detect, and maybe even prevent ASD are essential to reduce the burden of this condition.

Estrogen Receptor β as a Candidate Regulator of Sex Differences in the Maternal Immune Activation Model of ASD

“…The MIA model was developed based on the observation that infection during pregnancy is linked to ASD ( Atladottir et al, 2010 ; Zerbo et al, 2015 ; Al-Haddad et al, 2019 ). Outbreaks of several viruses, such rubella and influenza, have been documented to be associated with increased numbers of individuals with ASD ( Zerbo et al, 2013 ; Shuid et al, 2021 ). Consistent with these findings, the MIA model uses the injection of a toll-like receptor (TLR) ligand into pregnant wild-type female mice on a specific day of gestation to induce an immune response.…”

Maternal immune activation as a risk factor for psychiatric illness in the context of the SARS-CoV-2 pandemic

“…This suggests that the maternal immune response influences neurodevelopmental trajectory, altering offspring susceptibility to psychiatric illness ( al-Haddad et al., 2019 ). As suggested by the name, SARS-CoV-2 is largely defined by respiratory symptoms, lending face similarities to infections known to be associated with psychiatric illness risk ( Bordallo et al., 2020 ; Shuid et al., 2021 ). MIA via infection likely intersects with maternal stress and in the context of MIA due to SARS-CoV-2, these interacting factors are especially pertinent.…”

SARS-CoV-2-associated cytokine storm during pregnancy as a possible risk factor for neuropsychiatric disorder development in post-pandemic infants

“…Studies have reported that IL-1β, IL-6 and IL-17 are key molecules for infection-induced ASD ( Al-Ayadhi and Mostafa, 2012 ; Ashwood et al 2011a , 2011b ; Shuid et al, 2021 ), being the injection of either of these cytokines in animal models sufficient to trigger ASD-like behavior ( Favrais et al, 2011 ; T. Smith et al, 2007 ). Concerning the SARS-CoV-2 infection, one recent study found a concordant profile of inflammatory markers, particularly IL-6, IL-17 and tumor necrosis factor alpha (TNF-α), in peripheral blood of pregnant women as well as in the umbilical cord blood ( Fenizia et al, 2020 ).…”