Effectiveness of Non-Pharmacological Interventions for Fatigue in Long COVID: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
4 affiliations
- 1College of Integrated Chinese and Western Medicine, Changchun University of Traditional Chinese Medicine, Changchun 130117, China.
- 2Second Department of Pulmonary Diseases, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China.
- 3Department of Gastroenterology, Affiliated Hospital to Changchun University of Traditional Chinese Medicine, Changchun 130021, China.
- 4Department of Pneumology, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China.
Abstract
Background: Persistent fatigue is one of the most common and disabling symptoms of long COVID, yet no pharmacological treatments are currently established. Non-drug strategies are increasingly used, but evidence directly comparing these approaches remains limited. This systematic review and meta-analysis evaluated the effects of non-pharmacological interventions on fatigue in adults with long COVID and explored potential sources of heterogeneity. Materials and Methods: Following PRISMA 2020 and the Cochrane Handbook, we searched four databases from inception to December 2025 for RCTs comparing non-pharmacological interventions with control conditions in adults with WHO-defined long COVID. The primary outcome was pre-specified as fatigue severity; no secondary outcomes were pre-specified. Methodological quality was assessed using the RoB 2 tool. Random-effects models were used to pool SMDs, with exploratory subgroup, sensitivity, and publication bias analyses. Results: Thirteen RCTs (1276 participants) were included. Non-pharmacological interventions significantly reduced fatigue [SMD = -0.43, 95% CI: -0.68 to -0.18, p < 0.001], with substantial heterogeneity (I² = 72.1%). Subgroup analyses showed that exercise training yielded significant benefit [SMD = -0.64, 95% CI: -1.11 to -0.18, p = 0.006], whereas cognitive behavioural therapy, non-invasive neuromodulation, and nutritional supplementation did not reach statistical significance. Interventions lasting ≥8 weeks were associated with greater improvement (between-subgroup p = 0.027). Sensitivity analyses confirmed robustness, and no publication bias was detected. Conclusions: Non-pharmacological interventions, particularly exercise-based programmes, are associated with reduced fatigue in people with long COVID, with interventions lasting ≥8 weeks showing greater average improvements. Exercise-based rehabilitation currently has the most consistent evidence base among the evaluated modalities, although the difference in effects between intervention modalities was not statistically significant (p = 0.286). Further high-quality trials are required to determine the comparative effectiveness of emerging approaches and to identify optimal treatment strategies.
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BibTeX
@article{bi2026effectiveness,
title = {{Effectiveness of Non-Pharmacological Interventions for Fatigue in Long COVID: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}},
author = {Yanze Bi and Bo Yang and Siyu Chen and Qingrong Li and Rong Xu and Wenbo Zhang and Yunyi Yang and Wenshuang Zou and Shaodan Hu},
journal = {Healthcare (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/healthcare14203483},
url = {https://europepmc.org/article/MED/42940528},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effectiveness of Non-Pharmacological Interventions for Fatigue in Long COVID: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
AU - Yanze Bi
AU - Bo Yang
AU - Siyu Chen
AU - Qingrong Li
AU - Rong Xu
AU - Wenbo Zhang
AU - Yunyi Yang
AU - Wenshuang Zou
AU - Shaodan Hu
PY - 2026
DA - 2026/10/16
JO - Healthcare (Basel, Switzerland)
DO - 10.3390/healthcare14203483
UR - https://europepmc.org/article/MED/42940528
AB - Background: Persistent fatigue is one of the most common and disabling symptoms of long COVID, yet no pharmacological treatments are currently established. Non-drug strategies are increasingly used, but evidence directly comparing these approaches remains limited. This systematic review and meta-analysis evaluated the effects of non-pharmacological interventions on fatigue in adults with long COVID and explored potential sources of heterogeneity. Materials and Methods: Following PRISMA 2020 and the Cochrane Handbook, we searched four databases from inception to December 2025 for RCTs comparing non-pharmacological interventions with control conditions in adults with WHO-defined long COVID. The primary outcome was pre-specified as fatigue severity; no secondary outcomes were pre-specified. Methodological quality was assessed using the RoB 2 tool. Random-effects models were used to pool SMDs, with exploratory subgroup, sensitivity, and publication bias analyses. Results: Thirteen RCTs (1276 participants) were included. Non-pharmacological interventions significantly reduced fatigue [SMD = -0.43, 95% CI: -0.68 to -0.18, p < 0.001], with substantial heterogeneity (I² = 72.1%). Subgroup analyses showed that exercise training yielded significant benefit [SMD = -0.64, 95% CI: -1.11 to -0.18, p = 0.006], whereas cognitive behavioural therapy, non-invasive neuromodulation, and nutritional supplementation did not reach statistical significance. Interventions lasting ≥8 weeks were associated with greater improvement (between-subgroup p = 0.027). Sensitivity analyses confirmed robustness, and no publication bias was detected. Conclusions: Non-pharmacological interventions, particularly exercise-based programmes, are associated with reduced fatigue in people with long COVID, with interventions lasting ≥8 weeks showing greater average improvements. Exercise-based rehabilitation currently has the most consistent evidence base among the evaluated modalities, although the difference in effects between intervention modalities was not statistically significant (p = 0.286). Further high-quality trials are required to determine the comparative effectiveness of emerging approaches and to identify optimal treatment strategies.
SN - 2227-9032
ER -