Olfactory Training for Post-COVID-19 Olfactory Dysfunction: A Meta-Analysis of Efficacy and Combination Therapies.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 41010778 · doi:10.3390/jcm14186578
What was done
A systematic review and meta-analysis conducted according to PRISMA guidelines searched PubMed, Web of Science, and Ovid Medline through February 2025. Eight randomized controlled trials (RCTs) evaluating olfactory training (OT) using standardized protocols versus no treatment, placebo, or alternative therapies for post-COVID-19 olfactory dysfunction were included. Olfactory function was assessed using validated tests (UPSIT, Sniffin' Sticks TDI score, CCCRC, and B-SIT). Risk of bias was evaluated with the Joanna Briggs Institute appraisal tool.
What was found
Olfactory training significantly improved olfactory scores compared to controls. Combination therapies were associated with higher recovery rates (RR = 1.65, 95% CI: 1.13 to 2.42, p = 0.01). The largest improvement occurred when OT was combined with PEA-luteolin (MD = 4.62, 95% CI: 2.17 to 7.06, p = 0.0002), followed by EDTA (MD = 2.33, 95% CI: 0.58 to 4.08, p = 0.009). Corticosteroids demonstrated borderline benefit (MD = 1.34, 95% CI: 0.01 to 2.67, p = 0.05), whereas alpha-lipoic acid had no significant effect.
Why it matters
This meta-analysis consolidates randomized trial evidence confirming the efficacy of olfactory training for post-COVID-19 smell loss and identifies specific adjunct therapies, particularly PEA-luteolin, that may substantially augment recovery.
Limits
The total number of participants across the 8 included RCTs was not reported in the abstract. Subgroup analyses for specific adjunct therapies likely rely on very few trials. Potential heterogeneity across training regimens, durations, and diverse smell assessment scales limits direct comparison.