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

Chung et al., Brain Sciences, doi:10.3390/brainsci13071014, NCT04900415

Jun 2023

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Vitamin A for COVID-19

39th treatment shown to reduce risk in June 2023

^*, now known with p = 0.031 from 13 studies.

Lower risk for recovery and cases.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

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RCT 24 patients with olfactory dysfunction post-COVID-19 in Hong Kong, showing significantly improved recovery with the addition of vitamin A to aerosolised diffuser olfactory training. 25,000IU vitamin A for 14 days.

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relative BTT improvement, 75.1% better, RR 0.25, p = 0.048, treatment mean 3.01 (±2.52) n=9, control mean 0.75 (±1.67) n=8, vitamin A + OT vs. OT.

anosmia, 68.0% lower, RR 0.32, p = 0.47, treatment 0 of 9 (0.0%), control 1 of 8 (12.5%), NNT 8.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), vitamin A + OT vs. OT.

severe microsmia, 70.4% lower, RR 0.30, p = 0.29, treatment 1 of 9 (11.1%), control 3 of 8 (37.5%), NNT 3.8, vitamin A + OT vs. OT.

moderate microsmia, 74.6% lower, RR 0.25, p = 0.02, treatment 2 of 9 (22.2%), control 7 of 8 (87.5%), NNT 1.5, vitamin A + OT vs. OT.

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Chung et al., 30 Jun 2023, Randomized Controlled Trial, China, peer-reviewed, 14 authors, study period 14 August, 2020 - 11 June, 2021, trial NCT04900415 (history). Contact: tomwhc@hku.hk (corresponding author), ivanhung@hku.hk, makkf@hku.hk.

This Paper Vitamin A All

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

Tom Wai-Hin Chung, Hui Zhang, Fergus Kai-Chuen Wong, Siddharth Sridhar, Tatia Mei-Chun Lee, Gilberto Ka-Kit Leung, Koon-Ho Chan, Kui-Kai Lau, Anthony Raymond Tam, Deborah Tip-Yin Ho, Vincent Chi-Chung Cheng, Kwok-Yung Yuen, Ivan Fan-Ngai Hung, Henry Ka-Fung Mak

Brain Sciences, doi:10.3390/brainsci13071014

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

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