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

Abstract

A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.

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].…”

Case report: Transient symptoms of autism spectrum disorder in a 2‐year‐old boy

“…Ian was born just prior to the COVID‐19 pandemic but was not infected with the virus in utero or during his first years of life, which has been associated with neurodevelopmental delays in a small number of papers. 30 , 31 There are other reports of developmental delays in children born during the pandemic, 32 , 33 , 34 whether exposed to the virus or not, but no published reports of transient autism symptoms. Ian did not experience any significant changes in his exposure to other children or social situations in the short period over which the autism symptoms abated.…”

The Adverse Outcome Pathway Framework Applied to Neurological Symptoms of COVID-19

“…Two studies have observed placental invasion by immunohistochemical analysis and electron microscopy [ 125 , 126 ], and there are case reports which detected the virus in one infant and one fetus suffering from COVID-19 [ 127 , 128 ]. The concern for harmful effects on the developing brain due to SARS-CoV-2 remains, as it is well-documented that maternal infection is a risk factor for neurodevelopmental disorders including autism spectrum disorder and schizophrenia [ 129 , 130 , 131 , 132 ]. The main proposed key events are associated with the increased cytokine storm and hyperinflammation observed in pregnant women with COVID-19 and the loss of functional placenta integrity.…”