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

Author:

Chung Tom Wai-Hin1,Zhang Hui23ORCID,Wong Fergus Kai-Chuen4ORCID,Sridhar Siddharth156ORCID,Lee Tatia Mei-Chun78,Leung Gilberto Ka-Kit9,Chan Koon-Ho10,Lau Kui-Kai810,Tam Anthony Raymond10,Ho Deborah Tip-Yin10,Cheng Vincent Chi-Chung1ORCID,Yuen Kwok-Yung15611,Hung Ivan Fan-Ngai61011ORCID,Mak Henry Ka-Fung81213ORCID

Affiliation:

1. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

2. Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China

3. Research Institute for Intelligent Wearable Systems, The Hong Kong Polytechnic University, Hong Kong, China

4. Department of Ear, Nose and Throat, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China

5. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China

6. Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China

7. Department of Psychology, The University of Hong Kong, Hong Kong, China

8. State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China

9. Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

10. Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

11. The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China

12. Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

13. Alzheimer’s Disease Research Network, The University of Hong Kong, Hong Kong, China

Abstract

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.

Publisher

MDPI AG

Subject

General Neuroscience

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