Designing novel "Smell-Aids" to improve olfactory function in post COVID-19 era.

Background: Eyeglasses, hearing aids, etc., all serve to enhance the sensory stimuli to enable patients to see or hear things that they would not otherwise be able to, but we have no equivalent technology for olfaction, a pressing issue in the post-COVID era.

Methods: We attempt to invent "Smell-Aids" by non-invasively enhancing intranasal odorant delivery to the olfactory epithelium, using two prototypes: (a) a nasal foam plug with a diagonal channel embedded to direct air/odor flow upwards to the olfactory region; (b) a clip (similar to what synchronized swimmers use) pinching a critical nasal valve region that may intensify the nasal airflow vortex to the olfactory region.

Results: We first tested these prototypes in counter-balanced orders on 58 healthy subjects, where their measured odor detection thresholds to phenylethyl alcohol significantly improved with both prototypes in subjects with normal smell function (baseline: 8-16.5, n = 30, 12.49 ± 2.8, plug: 14.42 ± 4.9, pinch: 14.73 ± 5.4, p < 0.05), but not in subjects with "super" sensitivity at baseline (> 16.5, n = 28). Next, we tested the prototypes on 54 patients with confirmed olfactory losses (age 21-80 years, median 54.5), the majority of whom (37/54 = 69%) were post-COVID long haulers (infected 12/15/2019 to 10/4/23; persisted 30 to 1260 days, median 22 months). The remaining non-COVID smell losses (n = 17) span significantly longer from 5 months to 27 years (median 8.5 years). The 9-item NIH toolbox odor identification score significantly improved after application of both smell aids (baseline: 4.30 ± 2.27, plug 5.11 ± 2.32, pinch 4.82 ± 2.06, mixed model p < 0.05), especially among the non-COVID cohort. For COVID long haulers, only the nasal plug remained effective (p < 0.05). Subgroup analysis was performed on patients who reported diminished (hyposmia/anosmia 38/54) vs distorted smell (parosmia/phantosmia 27/54, n = 11 reported both) and showed that the nasal plug remains effective for both cohorts (p < 0.05) while the pinch is only effective for the hypo/anosmia cohort (p < 0.05).

Conclusions: These results preliminarily demonstrated the novelty of improving olfactory function through different peripheral mechanisms for different patient and normative cohorts and may one day lead to an effective over-the-counter smell aid. Enhancing olfactory functions in healthy and patient cohorts through improving intranasal air and odorant delivery.

Trial registration: ClinicalTrials.gov NCT05920330.