A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD needed. Methods: This pilot trial recruited COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences function by butanol threshold tests (BTT) between baseline end-of-treatment. Secondary outcomes included smell identification (SIT), structural MRI brain, serial seed-based functional connectivity (FC) analyses the cortical network resting-state (rs–fMRI). Results: total of 24 participants either combination (n = 10), standard care 9), control 5). Median duration 157 days (IQR 127–175). Mean BTT score 2.3 (SD 1.1). At end-of-treatment, mean scores significantly higher group than (p < 0.001, MD 4.4, 95% CI 1.7 7.2) 0.009) groups. Interval SIT increased group. rs–fMRI showed FC when compared other positive correlations found at left inferior frontal gyrus clinically significant improvements measured (r 0.858, p 0.001) 0.548, 0.042) Conclusions: Short-course VitA as