严重长期新冠后综合征中嗅觉训练疗效有限：一项前瞻性队列研究

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中文摘要

目的： 持续性化学感觉功能障碍是新冠后综合征（PCS）的一种令人衰弱的症状。虽然嗅觉训练（OT）对病毒感染后早期的嗅觉丧失有效，但其在慢性、多系统PCS中的疗效仍不明确。本研究旨在描述一个严重受累队列的特征，并评估在结构化OT干预期间嗅觉功能的变化。
方法： 在这项前瞻性研究中，从专门的新冠后门诊招募了29名持续性PCS超过12周（平均持续时间约30个月）的患者。所有患者均接受结构化OT（标准化每日两次暴露方案）12周。参与者在12周OT期前后接受了心理物理测试（Sniffin' Sticks TDI、味觉试纸）并完成了问卷（self-MOQ、VAS、EQ-5D-5 L）。
结果： 在纳入最终分析的25名患者中，9名根据TDI评分表现为心理物理性嗅觉缺失。该队列表现出高症状负担，健康相关生活质量低于人群常模。OT后，客观TDI评分未观察到统计学显著变化（19.0 ± 8.2 vs. 20.1 ± 10.5；p = 0.52）。同样，主观评分（VAS）和评估嗅觉生活质量的问卷在基线与随访之间也未显示显著差异。虽然报告了个别短暂改善，但观察到客观数据与主观感知之间持续存在差异。
结论： 在这一慢性PCS患者队列中，结构化嗅觉训练在12周观察期内未与可测量的改善相关。缺乏反应可能表明，在这一严重受累亚组中，嗅觉训练的有效性可能受到外周嗅觉功能障碍以外因素的限制，包括认知和功能能力下降。

英文摘要

PURPOSE: Persistent chemosensory dysfunction is a debilitating symptom of Post-COVID-19 Syndrome (PCS). While olfactory training (OT) is effective in early post-viral smell loss, its efficacy in chronic, multisystemic PCS remains unclear. This study aimed to characterize a severely affected cohort and to evaluate changes in olfactory function during a structured OT intervention.
METHODS: In this prospective study, 29 patients with persistent PCS lasting > 12 weeks (mean duration approximately 30 months) were recruited from a specialized post-COVID outpatient clinic. All patients underwent structured OT (standardized twice-daily exposure protocol) for 12 weeks. Participants underwent psychophysical testing (Sniffin' Sticks TDI, Taste Strips) and completed questionnaires (self-MOQ, VAS, EQ-5D-5 L) before and after a 12-week OT period.
RESULTS: Of 25 patients included in the final analysis, 9 presented with psychophysical anosmia based on the TDI score. The cohort exhibited a high symptom burden, with health-related quality of life below population norms. Following OT, no statistically significant changes were observed in the objective TDI scores (19.0 ± 8.2 vs. 20.1 ± 10.5; p = 0.52). Similarly, subjective ratings (VAS) and questionnaires assessing olfactory quality of life showed no significant differences between baseline and follow-up. While individual transient improvements were reported, a persistant discrepancy between objective data and subjective perception was observed.
CONCLUSION: Structured olfactory training was not associated with measurable improvement within the 12-week observation period in this cohort of chronic PCS patients. The lack of response may indicate that, in this severely affected subgroup, the effectiveness of olfactory training may be limited by factors beyond peripheral olfactory dysfunction, including reduced cognitive and functional capacity.