Integrative systemic characterization of the neuroimmunological interactions of Major Depressive Disorder and its intersection with post-COVID-19 syndrome

• Grant number: 23/12268-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): October 01, 2023
• Effective date (End): January 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Otávio Cabral Marques
• Grantee: Anny Silva Adri
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections, AP.JP

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic has left many psychopathological implications in COVID-19 survivors, such as depression, anxiety and cognitive impairments, which are now recognized as primary symptoms of "post-acute COVID-19 syndrome"11 . Depressive psychopathology has already been reported in about 35% of patients in short, medium and long-term follow-up after infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)12. Depressive symptoms associated with post-COVID-19 syndrome are known to increase fatigue and affect neurocognitive functioning, sleep, quality of life, and global functioning in COVID-19 survivors13. The psychopathological mechanisms underlying post-COVID-19 depressive symptoms are mainly related to the inflammation triggered by the peripheral immunoinflammatory response to the viral infection and the persistent psychological burden during and after the infection13. The large number of patients infected with SARS-CoV-2 and the high prevalence of post-COVID-19 depressive symptoms may significantly increase the group of people suffering from depressive disorders13,14. Therefore, screening, diagnosing, treating and monitoring the psychopathology of COVID-19 survivors is essential to counteract the disease burden of depression and years of life lived with disability. Thus, the objective of this project is to characterize new networks of neuroimmunological interactions associated with the pathophysiology of post-COVID-19 depressive disorders. Thus, an integrative analysis will be performed (eg, meta-analysis of data using Fisher's method followed by correction of the batch effect) of gene expression and proteomic datasets (of peripheral blood and central nervous system leukocytes) deposited in the ArrayExpress, Gene Expression Omnibus (GEO) and Proteome Exchange to identify possible biomarkers and predictors of severity (using machine learning techniques such as Random Forest) of greater relevance according to the investigated cohorts (patients with major depressive disorder [MDD] versus patients with post-COVID-19 syndrome), their networks of interactions (network and co-expression analysis) and correlations (bi- and multivariate correlations). In this way, this project will expand the current understanding of the pathophysiological factors that contribute to the understanding of psychoinflammation involved in MDD and individuals with post-COVID-19 syndrome, revealing new potential neuroimmunobiological therapeutic targets.