Neurotropic Manifestations as a Potential Risk Factor for Schizophrenia Following in utero Exposure to SARS-CoV-2

Background: COVID-19 infection is associated with neurologic and psychiatric morbidity that suggests a direct effect of the virus or secondary effect of an inflammatory process. These neuropsychiatric consequences may increase the likelihood of schizophrenia in the offspring of women who become infected with COVID-19 during their pregnancy. Methods: We performed a directed narrative review of the literature focusing on the proposed pathophysiological processes that lead to schizophrenia and known pathological consequences of COVID-19 infection. Results: Schizophrenia in adult offspring has been associated with maternal infections during pregnancy by a wide range of respiratory and neurotropic pathogens. Spikes in the incidence of schizophrenia approximately 20 years after several influenza pandemics have been documented. There are multiple lines of evidence suggesting that a similar pattern may be seen due to the recent COVID-19 pandemic. These include the nonspecific consequences of acute illness and hyperpyrexia, as well as more specific derangements of brain development related to direct effects of the virus or secondary effects of the inflammatory response on the developing brain. There is the potential to prospectively test this hypothesis by following the offspring of women who are known to have developed COVID-19 during their pregnancy. Conclusion: The COVID-19 pandemic is likely associated with a range of future neuropsychiatric consequences in people whose mothers suffered the infection during their fetal development. It is important to try to follow these offspring to determine the full range of consequences of COVID-19 infection.