Vestito Lucilla, Ponzano Marta, Mori Laura, Trompetto Carlo, Bandini Fabio
IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Heath (DINOGMI), University of Genoa, Genoa, Italy.
Department of Health Sciences, Section of Biostatistics, University of Genoa, Genoa, Italy.
Brain Stimul. 2025 Jul-Aug;18(4):1106-1112. doi: 10.1016/j.brs.2025.04.023. Epub 2025 May 8.
Persistent anosmia due to COVID-19 affects approximately 20 million individuals worldwide, with a serious detrimental effect on their quality of life. Effective treatments remain lacking, with olfactory training (OT) being supported by some evidence of benefit. We implemented a double-blind, randomized, controlled trial (RCT) combining OT with Anodal transcranial Direct Current Stimulation (A-tDCS) with the aim to confirm the encouraging results of a preliminary study by our group. We also evaluated the long-term effectiveness of this intervention at both one- and six-months post-treatment assessments.
This RCT involved 52 patients with persistent hypo/anosmia due to COVID-19. Participants were randomly assigned to undergo OT coupled with either A-tDCS targeting the Prefrontal Cortex (PFC) (experimental group, n = 35), or sham stimulation (placebo group, n = 17) for two weeks (10 sessions). The end point was the change in smell function from the baseline, as assessed by subjective and objective scores (VAS and Sniffin' Sticks test or SST).
The experimental group demonstrated a significant amelioration of both smell measures. Specifically, the mean VAS-smell increased from 2.56 to 4.70 (p < 0.001) and the mean SST from 6.97 to 9.69 (p < 0.001). Seventy-seven percent of patients in the experimental group significantly improved, with 63 % achieving a complete recovery. No olfactory amelioration was observed in the placebo group. The significant smell improvement was sustained at both follow-up assessments.
This RCT demonstrates that combining A-tDCS with concurrent OT is able to restore the olfactory function in individuals suffering from persistent COVID-19 anosmia, with a durable effect. This safe and inexpensive treatment can therefore represent a suitable and widespread option for millions of individuals. These positive results also support the hypothesis that the brain olfactory networks are involved in the pathophysiology of COVID-19 anosmia.
由新冠病毒病导致的持续性嗅觉丧失影响了全球约2000万人，对他们的生活质量造成了严重的不利影响。目前仍缺乏有效的治疗方法，嗅觉训练（OT）有一些获益证据支持。我们开展了一项双盲、随机、对照试验（RCT），将嗅觉训练与阳极经颅直流电刺激（A-tDCS）相结合，旨在证实我们团队一项初步研究的令人鼓舞的结果。我们还在治疗后1个月和6个月的评估中评估了这种干预措施的长期有效性。
这项RCT纳入了52例因新冠病毒病导致持续性嗅觉减退/丧失的患者。参与者被随机分配接受嗅觉训练，并同时接受针对前额叶皮质（PFC）的A-tDCS（实验组，n = 35），或假刺激（安慰剂组，n = 17），为期两周（10次疗程）。终点是通过主观和客观评分（视觉模拟量表[VAS]和嗅棒测试[SST]）评估的嗅觉功能相对于基线的变化。
实验组的两项嗅觉指标均有显著改善。具体而言，VAS嗅觉评分的平均值从2.56提高到4.70（p < 0.001），SST的平均值从6.97提高到9.69（p < 0.001）。实验组77%的患者有显著改善，63%的患者实现了完全康复。安慰剂组未观察到嗅觉改善。在两次随访评估中，嗅觉的显著改善均得以维持。
这项RCT表明，将A-tDCS与同步嗅觉训练相结合能够恢复新冠病毒病持续性嗅觉丧失患者的嗅觉功能，且效果持久。因此，这种安全且廉价的治疗方法可以成为数百万患者合适且广泛适用的选择。这些积极结果也支持了大脑嗅觉网络参与新冠病毒病嗅觉丧失病理生理学的假说。
