Tan Chang, Meng Jiahao, Dai Xingui, He Baimei, Liu Pan, Wu Yumei, Xiong Yilin, Yin Heng, Wang Shuhao, Gao Shuguang
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
EClinicalMedicine. 2025 Aug 5;87:103412. doi: 10.1016/j.eclinm.2025.103412. eCollection 2025 Sep.
BACKGROUND: Long COVID, characterized by persistent multi-organ symptoms post-SARS-CoV-2 infection, poses a substantial global health burden. While diverse therapeutic interventions have been proposed, their comparative efficacy remains uncertain due to fragmented evidence and methodological heterogeneity in prior studies. Therefore, we conducted a meta-analysis to comprehensively explore the effectiveness of diverse therapeutic interventions in long COVID. METHODS: In this meta-analysis, we searched PubMed, Cochrane Library, Embase, Web of Science, SPORTDiscus (EBSCO), CINAHL (EBSCO), and Rehabilitation & Sports medicine source (EBSCO) from inception to July 20, 2025, for randomized controlled trials (RCTs) evaluating exercise training, respiratory muscle training, telerehabilitation, transcranial direct current stimulation (tDCS), olfactory training, palmitoylethanolamide with luteolin (PEA-LUT), and steroid sprays in adults with Long COVID. Primary outcomes included cardiopulmonary function, exercise capacity, fatigue, and olfactory recovery. Data were pooled using random-effects models, with sensitivity analyses (leave-one-out method) and Egger's test to assess robustness and publication bias. GRADE criteria evaluated evidence certainty. The study was registered with PROSPERO (CRD42024591704). FINDINGS: We identified a total of 51 eligible trials, comprising 4026 participants. Significant differences were observed in the following outcomes in the context of exercise training: 6MWT (MD, 83.20; 95% CI 52.04-114.37), 30sSTS (MD, 3.05; 95% CI 1.96-4.13), SF-12 Mental Component Summary (SF-12-MCS) (MD, 3.10; 95% CI 0.78-5.43), VO2 peak (% predicted) (MD, 6.00; 95% CI 0.45-11.54), VO2 peak (L/kg/min) (MD, 1.61; 95% CI 0.40-2.81), VO2 peak (L/min) (MD, 0.14; 95% CI 0.03-0.25), mMRC dyspnea scale (MD, -1.04; 95% CI -1.73 to -0.35), the Multidimensional Functional Assessment of Daily Living Scale (MBDS) (MD, -4.61; 95% CI -8.19 to -1.03), and Visual Analogue Fatigue Scale (VAFS) (MD -1.69; 95% CI -3.07 to -0.31). Furthermore, significant differences were also found in the following key outcomes: 6MWT (MD, 89.54; 95% CI 9.86-169.23), MIP (% predicted) (MD, 15.79; 95% CI 2.73-28.84), MIP (cm HO) (MD, 19.69; 95% CI 10.14-29.24), and mMRC (MD, -1.02; 95% CI -1.86 to -0.18) in respiratory muscle training; 6MWT (MD 34.14; 95% CI 2.54-65.74), 30sSTS (MD 1.41; 95% CI 0.67-2.15), and FSS (MD -1.59; 95% CI -2.64 to -0.53) in telerehabilitation; MFIS-physical (MD, -2.29; 95% CI -4.36 to -0.22) in tDCS; and TDI Score (MD, 4.66; 95% CI 2.16-7.15) in PEA-LUT. INTERPRETATION: Exercise training should be prioritized for improving cardiopulmonary function and exercise capacity in Long COVID, supported by high-certainty evidence. Respiratory muscle training and PEA-LUT offer targeted benefits for respiratory strength and anosmia, while tDCS may address fatigue. Telerehabilitation, as a form of supervision, also improved the effectiveness of the intervention. In contrast, steroid sprays and olfactory training lack efficacy, highlighting the need for personalized, symptom-specific approaches. These findings advocate for updated clinical guidelines integrating multimodal therapies and underscore the urgency of large-scale trials to optimize dosing and long-term outcomes. FUNDING: This study was supported by the Hunan Provincial Natural Foundation of China (2021JJ30040), the National Key Research and Development Plan (2022YFC3601900, 2022YFC2505500), the National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University (2021KFJJ06), and the National Natural Science Foundation of China (No. 81672225).
背景:长新冠以感染SARS-CoV-2后持续出现多器官症状为特征,给全球健康带来了沉重负担。尽管已经提出了多种治疗干预措施,但由于先前研究中的证据零散和方法异质性,它们的相对疗效仍不确定。因此,我们进行了一项荟萃分析,以全面探讨多种治疗干预措施对长新冠的有效性。 方法:在这项荟萃分析中,我们检索了从创刊至2025年7月20日的PubMed、Cochrane图书馆、Embase、科学网、SPORTDiscus(EBSCO)、CINAHL(EBSCO)和康复与运动医学源(EBSCO),以查找评估运动训练、呼吸肌训练、远程康复、经颅直流电刺激(tDCS)、嗅觉训练、棕榈酰乙醇胺与木犀草素(PEA-LUT)以及类固醇喷雾剂对成年长新冠患者疗效的随机对照试验(RCT)。主要结局包括心肺功能、运动能力、疲劳和嗅觉恢复。使用随机效应模型汇总数据,并进行敏感性分析(留一法)和Egger检验以评估稳健性和发表偏倚。采用GRADE标准评估证据确定性。该研究已在PROSPERO(CRD42024591704)注册。 结果:我们共纳入了51项符合条件的试验,涉及4026名参与者。在运动训练方面,以下结局观察到显著差异:6分钟步行试验(MD,83.20;95%CI 52.04-114.37)、30秒坐站试验(MD,3.05;95%CI 1.96-4.13)、SF-12精神成分总结量表(SF-12-MCS)(MD,3.10;95%CI 0.78-5.43)、峰值摄氧量(预测值%)(MD,6.00;95%CI 0.45-11.54)、峰值摄氧量(L/kg/min)(MD,1.61;95%CI 0.40-2.81)、峰值摄氧量(L/min)(MD,0.14;95%CI 0.03-0.25)、改良英国医学研究委员会呼吸困难量表(MD,-1.04;95%CI -1.73至-0.35)、日常生活多维功能评估量表(MBDS)(MD,-4.61;95%CI -8.19至-1.03)以及视觉模拟疲劳量表(VAFS)(MD -1.69;95%CI -3.07至-0.31)。此外,在以下关键结局中也发现了显著差异:呼吸肌训练中的6分钟步行试验(MD,89.54;95%CI 9.86-169.23)、最大吸气压(预测值%)(MD,15.79;95%CI 2.73-28.84)、最大吸气压(cm H₂O)(MD,19.69;95%CI 10.14-29.24)以及改良英国医学研究委员会量表(MD,-1.02;95%CI -1.86至-0.18);远程康复中的6分钟步行试验(MD 34.14;95%CI 2.54-65.74)、30秒坐站试验(MD 1.41;95%CI 0.67-2.15)以及疲劳严重程度量表(MD -1.59;95%CI -2.64至-0.53);tDCS中的多维疲劳影响量表-身体维度(MD,-2.29;95%CI -4.36至-0.22);以及PEA-LUT中的嗅觉障碍检测问卷评分(MD,4.66;95%CI 2.16-7.15)。 解读:运动训练应以改善长新冠患者的心肺功能和运动能力为优先,这有高确定性证据支持。呼吸肌训练和PEA-LUT对呼吸力量和嗅觉丧失有针对性的益处,而tDCS可能有助于缓解疲劳。远程康复作为一种监督形式,也提高了干预效果。相比之下,类固醇喷雾剂和嗅觉训练缺乏疗效,这凸显了采用个性化、针对症状的方法的必要性。这些发现主张更新临床指南,纳入多模式疗法,并强调大规模试验以优化剂量和长期结局的紧迫性。 资金来源:本研究得到了中国湖南省自然科学基金(2021JJ30040)、国家重点研发计划(2022YFC3601900,2022YFC2505500)、中南大学湘雅医院国家老年疾病临床研究中心(2021KFJJ06)以及中国国家自然科学基金(No. 81672225)的支持。
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