COVID-19 has been strongly associated with olfactory dysfunction, including anosmia and hyposmia, which may persist as part of post-acute sequelae of SARS-CoV-2 infection (Long COVID). While early explanations focused on local damage to the olfactory epithelium, emerging evidence suggests that immune-mediated mechanisms and neuroinflammation play a critical role in both acute and persistent olfactory impairment. This review explores the potential contribution of G protein-coupled receptor (GPCR) dysregulation in SARS-CoV-2–related olfactory dysfunction, highlighting the interaction between viral infection, inflammatory signaling, and neuronal pathways. GPCRs are essential regulators of sensory perception, immune response modulation, and neuroimmune communication, and their disruption may contribute to altered olfactory signaling and prolonged recovery. In addition, cytokine-mediated inflammation, microglial activation, and neuroimmune imbalance may exacerbate olfactory pathway dysfunction. Understanding these mechanisms may provide insight into potential therapeutic strategies, including targeted anti-inflammatory interventions and GPCR-related pharmacological approaches. This article summarizes current evidence linking GPCR signaling and neuroinflammation to COVID-19–associated olfactory dysfunction and identifies key directions for future research.
Yersultan Musumankulov (Sun,) studied this question.