Clinical Improvement and Immune Signatures Following Platelet-Rich Plasma Therapy for Post-Viral Olfactory Dysfunction.

BACKGROUND: Platelet-rich plasma (PRP) has emerged as a promising therapy for post-viral olfactory dysfunction (PVOD) though its biological mechanisms remain unclear. This study evaluated clinical outcomes and targeted proteomic changes following PRP for refractory PVOD. METHODS: Adults with PVOD ≥ 6 months refractory to standard therapies underwent a single bilateral PRP injection into the olfactory clefts. Demographics, subjective olfactory ratings, and psychophysical assessment using the University of Pennsylvania Smell Identification Test (UPSIT) were obtained at baseline and follow-up. Paired olfactory cleft mucus samples were analyzed using the Olink Target 48 immune panel, and baseline cytokine profiles were compared with normosmic controls. RESULTS: Nineteen subjects were enrolled; 17 completed follow-ups. The mean baseline UPSIT was 19 with a median PVOD duration of 27 months. At a mean follow-up of 45 days, 47% reported subjective improvement and 53% achieved minimal clinically important difference. Mean UPSIT improved by +3.1 points (SD 6.0). Compared with controls, PVOD was associated with increased IL-18 and CCL13 expression. Following PRP, paired comparisons demonstrated increased CSF2 and IL-1β, and decreased IL-6 and IL-33. Pathway enrichment showed increased immune cell recruitment and tissue remodeling. Responders demonstrated increased oncostatin M (OSM) and a greater reduction in IL-17F, with concurrent within-subject increases in VEGFA and decreases in IL-6 and IL-33. CONCLUSION: PRP for refractory PVOD was associated with modest clinical improvement. Responder-specific analyses suggest PRP may promote coordinated immune remodeling characterized by reduction of inflammatory and epithelial stress signaling and activation of reparative pathways. These findings support biological plausibility and warrant further investigation.