Olfactory training for the treatment of COVID-19 related smell loss: a randomised double-blind controlled trial

Abstract

Background: Olfactory training is the most widely recommended treatment for smell loss; however, there are no randomised placebo-controlled trials evaluating its effectiveness in COVID-19. We aimed to evaluate the efficacy of isolated training and factors associated to olfactory recovery.

Methods: This is a prospective randomised double-blind controlled trial, using standard olfactory training (OT) and placebo (PB) in COVID-19 patients experiencing smell loss. They were followed up for 180 days and assessed with the Connecticut olfactory test (CCCRC) and with subjective methods on a monthly basis.

Results: A total of 123 participants completed follow-up: 68 in the OT group and 55 in the PB group. Overall, 84.5% achieved normosmia, with full recovery (FR) significantly higher in PB. At baseline, OT had lower olfactory scores and higher corticosteroid use. Multivariate analysis showed no significant differences in outcomes between groups. Baseline olfactory test scores were the strongest predictors of recovery. Exploratory analyses stratified participants by time to treatment initiation (early < 30 days; late > 30 days), showing a 58% higher chance of FR in the early group for similar CCCRC scores, regardless of management type.

Conclusions: OT is not superior to PB for treating COVID-19-related smell loss. Better results of first evaluation indicate great chance of full recovery and the use of systemic corticosteroid, in persistent olfactory loss, has not affected outcome.