Web-application guided bimodal olfactory training for COVID-19 patients: a randomized trial

Many Post-Acute COVID-19 Syndrome (PACS) patients continue to experience persistent dysosmia up to two years post-pandemic. Cognitive and semantic memory functions, along with olfactory associative areas, may be affected in PACS without olfactory recovery. Visual-olfactory bimodal olfactory training may stimulate these areas. This study evaluates the olfactory recovery using a new bi-modal training kit, MaMadeleine assisted by a web application.

A prospective randomised study (Nov 2021-June 2022) included PACS patients aged >=14 with post-infectious olfactory dysfunction. Patients were randomized for two months of simple (A) or semantic (B) visual-olfactory training. Evaluations included clinical assessments, Sniffin' Sticks Tests, and quality-of-life questionnaires. Adherence to treatment was monitored via the web application.

We included 83 patients, on average 13+-5.6 months after COVID-19. Olfactory training using MaMadeleine led to subjective orthoand retro-nasal olfactory improvement in 79.4% (n=58) and 58.9% (n=43) of patients, respectively, with Sniffin' Sticks Test scores increasing from 26.5+-7.5 to 29.1+-7.4. Both groups saw a 20% decrease in parosmia and phantosmia. No significant differences in recovery were observed between groups, although exploratory findings in a small subgroup (n=10) with semantic memory impairment suggest a possible benefit of bimodal training, warranting further investigation. Quality of life improved significantly in both groups. Adherence was better in group B than in group A.

MaMadeleine training improves subjective olfactory function, psychophysical test results, and quality of life in PACS patients with olfactory dysfunction. Multimodal training enhances adherence. Further studies are needed in semantic memory-impaired patients.