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

Abstract

Inflammation, due to infectious pathogens or other non-infectious stimuli, during pregnancy is associated with elevated risk for neurodevelopmental disorders such as schizophrenia and autism in the offspring. Although historically identified through retrospective epidemiologic studies, the relationship between maternal immune activation and offspring neurodevelopmental disease risk is now well established because of clinical studies which utilized prospective birth cohorts, serologically confirmed infection records, and subsequent long-term offspring follow-up. These efforts have been corroborated by preclinical research which demonstrates anatomical, biochemical, and behavioural alterations that resemble the clinical features of psychiatric illnesses. Intervention studies further demonstrate causal roles of inflammatory mediators, such as cytokines, in these long-lasting changes in behaviour and brain. This review summarizes a selection of maternal immune activation literature that explores the relationship between these inflammatory mediators and the neuropsychiatric-like effects later observed in the offspring. This literature is presented alongside emerging information regarding SARS-CoV-2 infection in pregnancy, with discussion of how these data may inform future research regarding the effects of the present coronavirus pandemic on emerging birth cohorts.

COVID-19 in pregnancy: implications for fetal brain development

“…The potential for neurodevelopmental morbidity in offspring exposed prenatally to SARS-CoV-2 is therefore of great concern. Given the large number of exposed individuals, even a modest increase in risk for adverse offspring neurodevelopment would still have a massive public health impact [15][16][17][18][19][20]. More than 59 million people in the United States and 300 million worldwide have been diagnosed with coronavirus disease 2019 (COVID-19) i , including over 155 500 pregnant women in the United States [21].…”

Effects of COVID-19 on children with autism

“…The etiology of autism is multifactorial, with interacting genetic and environmental factors. Maternal immune activation is a significant risk factor for the offspring's neurodevelopmental diseases such as schizophrenia and autism[ 47 ]. Children with autism are more liable to many mental health disorders such as depression, sleep disorders, addiction, attention deficit, and hyperactivity behaviors since the COVID-19 pandemic started[ 48 ] (Panda).…”

COVID-19 – prime time for microphysiological systems, as illustrated for the brain

“…Virus infections and the resulting inflammatory responses are known risk factors for autism spectrum disorders (ASD) (Shuid et al, 2021;Lins, 2021) and, with definitive diagnoses only two to three years after birth, time will tell whether COVID-19 infection fuels ASD or other neurodevelopmental disorders in children born to SARS-CoV-2-infected mothers. Stem cell-derived organoid models could address such possible neurodevelopmental hazards.…”