A Randomized Controlled Trial on the Management of Post-COVID-19 Olfactory Dysfunction in a Pediatric Population

Olfactory impairment is an important sequela of SARS-CoV-2 infection with potential long-term implications. Of treatments posited for post-COVID-19 olfactory dysfunction (OD), the strongest evidence supports olfactory training (OT) and topical steroids; however, a direct comparison of these treatments has yet to be published. Our objective was to directly compare the efficacy of OT versus budesonide irrigations for the treatment of post-COVID-19 OD in a pediatric population.  Methods: Pediatric patients aged six to 21 years presenting to the University of Pittsburgh, a tertiary children's hospital in Pittsburgh, Pennsylvania, between September 2021 and May 2023 with at least eight weeks of smell dysfunction following COVID-19 infection were eligible. Participants were randomized (parallel, non-blinded) to 1) OT or 2) OT with budesonide irrigations (OT+BI) for eight weeks. Participants completed a University of Pennsylvania Smell Identification Test (UPSIT) and 22-item Sinonasal Outcome Test (SNOT-22) upon enrollment and eight-week follow-up.  Results: Twenty participants (75% female, median 16.0 years, range 7-19 years) were included, with 11 participants in the OT arm and nine in the OT+BI arm. The median time from COVID-19 infection to clinic presentation was 279.5 days (range 60-952 days). The OT arm did not show significant improvement in SNOT-22 or UPSIT scores at the eight-week follow-up, with limited follow-up data for the OT+BI irrigation arm.  Conclusions: We present the first randomized clinical trial comparing OT and topical steroids for the management of post-COVID-19 OD in a pediatric population. Although the participants did not show significant improvement in olfactory outcomes at eight weeks, hypothetically, longer treatment times may be warranted. This study was limited by a small sample size and high attrition, particularly in the intervention arm, which restricts the strength of our conclusions.