Positive long-term outcomes of functional nasal surgery and histological findings in post-COVID-19 olfactory dysfunction

Background: Olfactory dysfunction (OD) is common in COVID-19 and in a small percentage of patients it can become persistent, substantially impacting on quality of life. Effective treatment options for persistent COVID-19-related OD (C19OD) remain limited. Functional septorhinoplasty (fSRP) can improve olfaction in persistent C19OD by increasing nasal airflow to the olfactory cleft and improving olfactory epithelium (OE) stimulation. However, this implies a retained and functioning OE in C19OD patients. This study evaluates the 12-month outcomes of fSRP and investigates the histopathological correlates supporting the role of nasal airflow improvement to restore olfaction. Methods: This observational cohort study enrolled 12 patients with persistent C19OD who underwent fSRP. Olfactory function (Sniffin Sticks TDI scores) and nasal airflow were assessed at baseline, 3, 6, and 12 months. Endoscopic olfactory mucosa biopsies were obtained at baseline from 8 patients for immunohistochemical analysis. Results: fSRP led to statistically significant and clinically relevant TDI improvements at 12 months (median improvement 8.0 from baseline, p<0.005) accompanied by sustained improvement of nasal airflow (p=0.01). Histological analysis showed the presence of immature and mature olfactory sensory neurons in 3 patients (37.5%). In one specimen, intact OE was identified containing horizontal basal cells, indicating preserved regenerative capacity more than two years post-infection. Conclusions: fSRP provides sustained clinical benefits for patients with persistent C19OD. The survival of sensory neurons and progenitor cells in the olfactory mucosa beyond two years suggests a biological substrate for olfactory recovery, which may be facilitated by surgically improved nasal airflow and OE stimulation.