Association between influenza A virus and SARS-CoV-2 infections and mood disorders

Acute respiratory infections (ARIs) are among the most common infectious diseases encountered in clinical practice, with approximately 70-80 % of cases attributed to viral pathogens. Among these, seasonal influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistently pose public health threats due to their high genetic variability, strong transmissibility and significant pathogenicity. Recently, accumulating evidence has suggested that these viruses can not only cause typical respiratory symptoms but also affect the central nervous system (CNS) through neuroinvasion and inflammation, thereby increasing the risk of developing or exacerbating mood disorders such as anxiety and depression. This makes them significant complications affecting patient prognosis and public health resources. This comorbidity between infection and mood disorders exhibits a complex bidirectional relationship. Beyond viral CNS involvement, individuals with mood disorders appear to be more susceptible to IAV and SARS-CoV-2 infections and may be at greater risk of developing severe illness. This comorbidity not only significantly impairs quality of life and clinical outcomes but also places a substantial burden on healthcare systems and public health infrastructure. Therefore, this review aims to summarize the clinical characteristics of IAV and SARS-CoV-2 infections comorbid with mood disorders. Based on existing evidence, we innovatively distinguish two mechanism pathways: an externally driven pathway dominated by psychological stress (acute stress), and an internal biological pathway represented by immune dysregulation and gut microbiota imbalance. This classification will provide a theoretical framework and research direction for accurately identifying acute stress responses and persistent neuropathology, as well as for future basic research and targeted intervention strategies.