Patients with COVID-19 olfactory loss benefit from visual-olfactory training

Current evidence for pharmacological intervention showing consistent benefit for COVID-19–associated PVOD is weak, with very few controlled studies that account for spontaneous recovery over time. One proposed beneficial treatment for postviral OL is olfactory training (OT).

Dual-sensory stimulation training has been shown to enhance a variety of different sensory and cognitive processes, including auditory adaption process. Data suggest that multisensory integration through the addition of a visual component to OT may potentiate olfactory neuroplasticity by stimulating cross-modal sensory transfer. Authors aimed to increase adherence to OT by enabling participants to select their own essential oils with which to perform OT. The objective of this study was to determine the efficacy of bimodal (visual-olfactory) training vs unimodal training and the efficacy of patient-preferred vs physician-assigned scents for COVID-19 PVOD.

This was a randomized, single-blinded trial with a 2-by-2 factorial design (bimodal, patient preferred; unimodal, physician assigned; bimodal, physician assigned; unimodal, patient preferred) and an independent control group. Enrollment occurred from February 1 to May 27, 2021. Participants were adults 18 to 71 years old with current olfactory loss defined as University of Pennsylvania Smell Identification Test (UPSIT) score less than 34 for men and less than 35 for women and duration of 3 months or longer. Olfactory loss was initially diagnosed within 2 weeks of COVID-19 infection.

Participants sniffed 4 essential oils for 15 seconds with a 30-second rest in between odors for 3 months. Participants in the physician-assigned odor arms trained with rose, lemon, eucalyptus, and clove. Participants randomized to the patient-preferred arms chose 4 of 24 available scents. If assigned to the bimodal arm, participants were shown digital images of the essential oil they were smelling.

The primary end point was post intervention change in UPSIT score from baseline; measures used were the UPSIT (validated, objective psychometric test of olfaction), Clinical Global Impressions Impression–Improvement (CGI-I; self-report improvement scale), and Olfactory Dysfunction Outcomes Rating (ODOR; olfaction-related quality-of-life questionnaire).

Among the 275 enrolled participants, the mean (SD) age was 41 (12) years, and 236 (86%) were female. The change in UPSIT scores preintervention to postintervention was similar between the study arms. The marginal mean difference for change in UPSIT scores preintervention to postintervention between participants randomized to patient-preferred vs physician-assigned olfactory training was 0.73 (95% CI, −1.10 to 2.56), and between participants randomized to bimodal vs unimodal olfactory training was 1.10 (95% CI, −2.92 to 0.74).

Five (24%) participants in the control arm had clinically important improvement on UPSIT compared with 18 (53%) in the bimodal, patient-preferred arm for a difference of 29% (95% CI, 4%-54%).

Four (19%) participants in the control group self-reported improvement on CGI-I compared with 12 (35%) in the bimodal, patient-preferred arm for a difference of 16% (95% CI, −7% to 39%).

The mean change in ODOR score preintervention to postintervention was 11.6 points (95% CI, 9.2-13.9), which was not deemed clinically important nor significantly different between arms.

In this randomized clinical trial, authors found that olfactory function improved over time in both the control and intervention arms, and that no clinically meaningful difference was observed in the mean change in the UPSIT score between the 4 intervention arms and even when they were compared with the control group. Furthermore, no meaningful difference was observed between participants randomized to the bimodal arms or unimodal arms and no difference between participants who were able to pick their own essential oils and those who were assigned the traditional 4 odors.

However, when the percentage of participants who experienced a clinically meaningful improvement in UPSIT score was defined and compared between groups, the highest percentage of participants experiencing improvement was in the bimodal arms. The unimodal training with physician assigned OT and the control arms had the smallest percentage of responders.

The arm with the largest percentage of participants self-reporting improvement (CGI-I) was the bimodal training with physician-assigned scents arm, with more than twice the percentage of responders than the control group. The change in ODOR score was not clinically important nor different between intervention arms. While not definitive nor consistent across the 3 outcome measures, the result of this study suggests that individuals with OL may benefit from OT.

In this randomized clinical trial, results failed to show benefit of OT as measured by UPSIT for patients with OL. However, many patients experienced and self-reported clinically important improvement in olfaction, suggesting that patients with COVID19–related OL may benefit from OT. Furthermore, potential benefit may be obtained from addition of a visual component to OT. While natural improvement does occur, the low-cost, noninvasive nature and minimal risk of OT suggests that physicians should recommend this treatment to patients with PVOD, as it may provide incremental benefit. Future studies should focus on identifying strata of the population for whom OT is likely to be beneficial alone or in combination with other potential treatments

Source: Amish M. Khan; Jeffrey Piccirillo; Dorina Kallogjeri; Jay F. Piccirillo; JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2022.4112