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.

Keywords: Autism; Brain; Development; Pregnancy; SARS-CoV-2; Schizophrenia.

Fig. 1

Possible mechanisms associated with deleterious consequences of SARS-CoV-2 infection during pregnancy. As previously shown for other viral infections, the direct infection of the fetal brain (A) or maternal immune response associated with infection (B) may have persistent effects on the developing brain (C). Cytokine storm syndrome, characterized by high levels of proinflammatory mediators is experienced by COVID-19 patients. Several proinflammatory markers associated with the cytokine storm were shown to influence synapse pruning and susceptibility of neurodevelopmental disorders, including autism spectrum disorder (ASD) and schizophrenia (SZ).