Immune Response Is Key to Genetic Mechanisms of SARS-CoV-2 Infection With Psychiatric Disorders Based on Differential Gene Expression Pattern Analysis

Abstract

Existing evidence demonstrates that coronavirus disease 2019 (COVID-19) leads to psychiatric illness, despite its main clinical manifestations affecting the respiratory system. People with mental disorders are more susceptible to COVID-19 than individuals without coexisting mental health disorders, with significantly higher rates of severe illness and mortality in this population. The incidence of new psychiatric diagnoses after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also remarkably high. SARS-CoV-2 has been reported to use angiotensin-converting enzyme-2 (ACE2) as a receptor for infecting susceptible cells and is expressed in various tissues, including brain tissue. Thus, there is an urgent need to investigate the mechanism linking psychiatric disorders to COVID-19. Using a data set of peripheral blood cells from patients with COVID-19, we compared this to data sets of whole blood collected from patients with psychiatric disorders and used bioinformatics and systems biology approaches to identify genetic links. We found a large number of overlapping immune-related genes between patients infected with SARS-CoV-2 and differentially expressed genes of bipolar disorder (BD), schizophrenia (SZ), and late-onset major depressive disorder (LOD). Many pathways closely related to inflammatory responses, such as MAPK, PPAR, and TGF-β signaling pathways, were observed by enrichment analysis of common differentially expressed genes (DEGs). We also performed a comprehensive analysis of protein–protein interaction network and gene regulation networks. Chemical–protein interaction networks and drug prediction were used to screen potential pharmacologic therapies. We hope that by elucidating the relationship between the pathogenetic processes and genetic mechanisms of infection with SARS-CoV-2 with psychiatric disorders, it will lead to innovative strategies for future research and treatment of psychiatric disorders linked to COVID-19.