In Silico Analysis Reveals Overlapping Molecular Mechanisms Between COVID-19 and Attention-Deficit/Hyperactivity Disorder

Abstract

Background: Coronavirus disease 2019 (COVID-19) has been increasingly associated with neurological complications, mainly through mechanisms involving neuroinflammation and cytokine dysregulation. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder with known immunological and neurotrophic components, has emerged as a potential risk factor for adverse COVID-19 outcomes. This study investigates the genetic interplay between COVID-19 and ADHD using in silico methods, aiming to identify shared molecular pathways and uncover convergent mechanisms that may inform pathophysiology, risk stratification, and potential therapeutic interventions. Methods: Genes associated with COVID-19 and ADHD were retrieved from the DisGeNET database. Shared genes were identified using FunRich software, and protein-protein interactions were analyzed using the Search Tool for Retrieval of Interacting Genes database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to further elucidate the shared molecular mechanisms. Results: Overall, 216 overlapping genes, including key genes, such as neuropilin-1, brain-derived neurotrophic factor, insulin-like growth factor 1, and interleukin-6, were identified. These genes were involved in three key functional categories: (1) vascular and endothelial function, (2) neurodevelopment and synaptic activity, and (3) immune modulation and inflammatory response generation. These findings indicate the potential shared molecular mechanisms between COVID-19 and ADHD. Conclusions: The identified overlapping genes highlight potential therapeutic targets for both conditions. The study underscores the significance of their shared molecular pathways and proposes the use of animal models to validate these genetic associations. Further investigation into these pathways may inform strategies for disease prevention and management of COVID-19 and ADHD.