Introduction: The aim of this randomized, single-blinded, placebo-controlled pilot study was to explore the feasibility, acceptance and effects of pulsed electromagnetic field therapy (PEMF) in patients with 
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Methods: A total of 20 patients were included in the study. They were randomly assigned to an intervention group (n = 10, male:female = 4 : 5, age = 45 ± 9 years) and a placebo group (n = 10, m:f = 4:6, age: 39 ± 23 years). A Papimi™ Delta professional electromagnetic field therapy device was used for treatment. Controls received a placebo PEMF. In total 10 PEMF sessions (30 min., 2× per week) were applied. Physical performance, health-related quality of life, fatigue, work ability, sleep, pain, anxiety and depression were assessed at baseline, posttreatment and at follow-up 5 weeks after treatment. Feasibility and acceptance were assessed posttreatment.
Results: The intervention group showed a notable improvement in the 6 minutes walking test. The use of PEMF improved fatigue (measured with the Brief Fatigue Inventory and the Multidimensional Fatigue Inventory). Also, the depression subscale of the Hospital Anxiety and Depression Scale, the Insomnia Severity Index, the Work Ability Index and most subscales of the Short Form (SF) 36 questionnaire showed improvement. From the placebo group three patients dropped out. There were no drop-outs in the intervention group. In the intervention group, PEMF was well-accepted and patients showed very good adherence.
Discussion
The PEMF can be applied to treat a variety of disorders. The advantages of PEMF seem to be that the intervention is noninvasive and no serious side effects, such as post-exertional malaise are known. Growing evidence from clinical studies and clinical routine suggests that ion induction therapy may be effective for osteoarthritis, inflammation and accelerated regeneration. It has also been shown to enhance bone fracture healing and alleviate low back pain [27,28,29,30,31,32,33].
In the present study, the Papimi™ Delta professional electromagnetic field therapy device (Pulse Dynamics Ltd., Pipinou 1 & Souliou, 17342 Agios Dimitrios, Greece) was used for treatment [10]. Pulsed electromagnetic field therapy (PEMF) is used to treat different pathologies of bones, muscles and joints [27,28,29,30,31,32,33]. It provides a cost-effective and safe therapeutic modality with growing popularity and use in physical medicine and rehabilitation. We daily use PEMF in common clinical practice for several musculoskeletal pain disorders.
In patients suffering from fatigue, PEMF treatment has been applied in patients with multiple sclerosis with mixed success [34, 35]; however, previous studies on multiple sclerosis-associated fatigue were performed using heterogeneous treatment parameters.
The scientific literature on magnetic field therapy for COVID-19 and post-COVID-19 fatigue is still rare.
In a study of patients with COVID-19 pneumonia, low-frequency PEMF therapy was successfully used to reduce respiratory symptoms, pain, anxiety and depression, and improve quality of life [36].
Zhang et al. recently performed a case report on transcranial magnetic stimulation using the electromagnetic brain pulse technique (frequency: 9–15 Hz, flux density: 0.6 T) in a patient with long COVID. After 10 therapy sessions, the patient had improvements in mood, sense of smell, and brain fogging [37].
In a further case report by Schaefer et al., PEMF (frequency of 550 Hz, flux density: 1 mT) was applied once at the area of the stellate ganglion [39]. Immediately post-treatment isometric muscle strength of hip flexors and elbow flexors improved and the subjective long COVID symptoms resolved the following day. At 6 months the patient’s long COVID symptoms have not returned [38].
In 2022 a case report on the use of PEMF for post-COVID-19-related fatigue was published by our working group [8]. After 5 weeks of PEMF, notable improvements were observed in fatigue, work ability, HRQOL and mental well-being. The positive results were maintained 6 weeks post-treatment.
The three reported case reports used very heterogeneous therapy protocols. Therefore, they cannot be compared to each other [8, 37, 38].
The present study aimed to describe the feasibility and acceptance of an intervention by using PEMF with the goal to improve symptoms related to post-COVID-19 fatigue syndrome.
The results showed that PEMF was both feasible and well accepted. Patients in the intervention group showed excellent compliance and adherence, with only 5% of 100 sessions missed in the intervention group, compared to 10% of 70 sessions missed in the placebo group. Additionally, there were three drop-outs in the placebo group due to increased fatigue, whereas no participants dropped out of the intervention group, indicating that real PEMF was well tolerated. Moreover, no patients in the intervention group experienced worsening of their condition.
Additionally, this intervention successfully reduced fatigue, improved physical performance and work ability, sleep quality and enhanced most aspects of HRQOL in the intervention group (Table 2).
The benefits of PEMF therapy extended beyond the initial treatment, with sustained improvements observed in physical activities, mental health, sleep quality, overall quality of life and work ability (Table 2). These results seem to be in accordance with the theory that PEMF (as with other physical stimuli) might enhance tissue regeneration [27, 32]. Furthermore, repetitive exposure to PEMF might notably improve mitochondrial function, which has been damaged by hyperinflammation [37, 39].
The intervention group improved less in T1 concerning “role physical” and “mental health” but at T2, both parameters notably changed in favor of the intervention group.
There was no difference between the groups in the 30 s STS and hand grip strength, while the 6 MWT results demonstrated significant improvements favoring the intervention group. These findings suggest that PEMF may impact aerobic capacity rather than muscle strength, potentially supporting the idea that PEMF can enhance mitochondrial function [39].
The minimal clinically important difference (MCID) is defined as the smallest change in score that patients perceive as beneficial [40].
For a number of outcomes presented in this paper, there is no agreed MCID but we only know that a certain direction is preferable (e.g., it is preferable to be able to walk further). Therefore, we believe that it is scientifically sound to add MCIDs and binary values based on these MCIDs only when there is an overwhelming scientific consensus.
The available literature with respect to rehabilitation of patients with post-COVID-19 suggests a MCID for 6 MWT of more than 35 m for adult patients with cardiopulmonary diseases [40]. In our study, the 6 MWT improved for the intervention group at T1 by 55 m and at T2 by 79 m. The placebo group worsened at T1 by 246m and improved at T2 by 40 m. These results indicate a clinical benefit after PEMF [40].
Furthermore, the MFI total score improved notably at T2 after real PEMF by 20.5 units. The MCID for the MFI total score was suggested to be −14.3 units [40].
Unfortunately, for the remaining parameters there are no data with respect to MCID in patients suffering from post-COVID-19 fatigue syndrome.
The HADS anxiety subscale and current pain (assessed with the numeric rating scale of the PD-Q) showed no benefit for the intervention group. These results suggest that PEMF might not have a measurable short-term effect on these parameters in patients suffering from post-COVID-19.
In summary, PEMF seems to be an effective approach, which can be embedded into the comprehensive multimodal and interdisciplinary rehabilitation concept of certain patients suffering from post-COVID-19 fatigue syndrome [41, 42].
The present study has several limitations. This was a pilot study with a limited statistical power showing the changes in a descriptive matter. Nevertheless, this was the first randomized, placebo-controlled trial, in which feasibility and acceptance as well as the effectiveness of PEMF for post-COVID-19 fatigue syndrome was demonstrated.
Conclusion
The results of this pilot study indicate safe feasibility and good acceptance of PEMF for patients with post-COVID-19 fatigue syndrome. Furthermore, this study population showed improvements in physical and mental health in the intervention group. This study seems to be an important contribution to this growing research field and provides the required evidence for future larger randomized controlled efficacy studies on PEMF in post-COVID-19 patients.
Nevertheless, further research including high-quality randomized controlled clinical trials should focus on effects of PEMF on patients with post-COVID-19 fatigue syndrome.
