Chung Tom Wai-Hin, Zhang Hui, Wong Fergus Kai-Chuen, Sridhar Siddharth, Lee Tatia Mei-Chun, Leung Gilberto Ka-Kit, Chan Koon-Ho, Lau Kui-Kai, Tam Anthony Raymond, Ho Deborah Tip-Yin, Cheng Vincent Chi-Chung, Yuen Kwok-Yung, Hung Ivan Fan-Ngai, Mak Henry Ka-Fung
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China.
Brain Sci. 2023 Jun 30;13(7):1014. doi: 10.3390/brainsci13071014.
Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. 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). A total of 24 participants were randomly assigned to receive either combination treatment ( = 10), standard care ( = 9), or control ( = 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 ( < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care ( = 0.009) groups. Interval SIT scores increased significantly ( = 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, < 0.001) and SIT ( = 0.548, = 0.042) scores for the combination group. Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.
嗅觉功能障碍（OD）是长期新冠后遗症中一种常见的神经感觉表现。需要一种针对与新冠相关的嗅觉功能障碍的有效且安全的治疗方法。这项试点试验招募了患有持续性嗅觉功能障碍的长期新冠后遗症患者。参与者被随机分配接受为期14天的短期口服维生素A（维生素A；每天25,000国际单位）和气雾扩散器嗅觉训练（OT），每天三次（联合治疗组），单独接受OT（标准治疗组），或观察（对照组），为期4周。主要结局是通过丁醇阈值测试（BTT）评估的治疗基线与治疗结束时嗅觉功能的差异。次要结局包括嗅觉识别测试（SIT）、脑部结构磁共振成像（MRI），以及通过静息态功能磁共振成像（rs-fMRI）对嗅觉皮质网络进行的基于种子点的系列功能连接（FC）分析。共有24名参与者被随机分配接受联合治疗（n = 10）、标准治疗（n = 9）或对照（n = 5）。嗅觉功能障碍的中位持续时间为157天（四分位间距127 - 175天）。基线BTT平均得分为2.3（标准差1.1）。治疗结束时，联合治疗组的平均BTT得分显著高于对照组（P < 0.001，平均差 = 4.4，95%置信区间1.7至7.2）和标准治疗组（P = 0.009）。联合治疗组的间隔SIT得分显著增加（P = 0.009）。与其他组相比，rs-fMRI显示联合治疗组的功能连接显著更高。治疗结束时，联合治疗组左下额回功能连接增加与测量的BTT（r = 0.858，P < 0.001）和SIT（P = 0.548，P = 0.042）得分的临床显著改善之间存在正相关。短期口服维生素A和气雾扩散器嗅觉训练联合治疗对长期新冠后遗症中的持续性嗅觉功能障碍有效。
