Journal Article

Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial

Cocuzza, Salvatore, Ingrassia, Angelo, Gaino, Francesca, Pace, Gian Marco, Ferreli, Fabio, Mercante, Giuseppe, De Luca, Pietro, Di Stadio, Arianna, Gallina, Salvatore, La Mantia, Ignazio, Brenner, Michael J., Oliva, Simone, Camaioni, Angelo, Sireci, Federico

2023

Overview

Purpose Few evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA–LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19. Methods This double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of > 6 month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA–LUT alone; (3) twice daily um-PEA–LUT alone; or (4) combination of once daily um-PEA–LUT with olfactory training. Olfactory testing (Sniffin’ Sticks odor identification test) was performed at baseline and at 1, 2, and 3 months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at T 0 , T 1 , T 2 and T 3 across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data. Results All patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA–LUT alone, and 41.6% receiving once daily um-PEA–LUT alone ( p  < 0.00001). Patients receiving treatment with um-PEA–LUT alone demonstrated subclinical improvement (< 3 point odor identification improvement) more often than patients receiving olfactory training with placebo ( p  < 0.0001.) Conclusions Olfactory training plus once daily um-PEA–LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19. Trial registration 20112020PGFN on clinicaltrials.gov. Level of evidence 1b (Individual Randomized Clinical Trial).

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: COVID-19 - complications / Head and Neck Surgery / Humans / Luteolin / Medicine / Medicine & Public Health / Neurosurgery / Olfaction Disorders - drug therapy / Olfaction Disorders - etiology / Olfactory Training / Otorhinolaryngology / Rhinology / Smell