COVID Olfactory Dysfunction: The Role of GPCR Dysregulation and Neuroinflammation

This project presents a hypothesis-driven conceptual framework addressing the mechanisms underlying COVID-19–associated olfactory dysfunction. While olfactory impairment is a common and often persistent symptom of SARS-CoV-2 infection, its pathophysiological basis remains incompletely understood, particularly in cases without overt structural damage to the olfactory epithelium or central nervous system. Based on existing clinical, molecular, and neurobiological evidence, this manuscript proposes that dysregulation of G-protein-coupled receptor (GPCR) signaling, combined with neuroinflammatory processes, may represent a key mechanistic link contributing to transient and long-term olfactory dysfunction in COVID-19. The framework integrates current findings on GPCR signaling pathways, immune-mediated inflammation, and neuronal signaling alterations to generate testable hypotheses. This work does not present new experimental or clinical data but aims to provide a structured theoretical model that may guide future experimental, translational, and clinical research into post-viral olfactory disorders, including long COVID–associated sensory deficits.