Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study

Abstract

Fatigue is one of the most frequent and disabling symptoms of post-COVID syndrome. In this study, we aimed to assess the effects of transcranial direct current stimulation on fatigue severity in a group of patients with post-COVID syndrome and chronic fatigue. We conducted a double-blind, parallel-group, sham-controlled study to evaluate the short-term effects of anodal transcranial direct current stimulation (2 mA, 20 min/day) on the left dorsolateral prefrontal cortex. The Modified Fatigue Impact Scale score was used as the primary endpoint. Secondary endpoints included cognition (Stroop test), depressive symptoms (Beck Depression Inventory), and quality of life (EuroQol-5D). Patients received eight sessions of transcranial direct current stimulation and were evaluated at baseline, immediately after the last session, and one month later. Forty-seven patients were enrolled (23 in the active treatment group and 24 in the sham treatment group); mean age was 45.66 ± 9.49 years, and 37 (78.72%) were women. The mean progression time since acute infection was 20.68 ± 6.34 months. Active transcranial direct current stimulation was associated with a statistically significant improvement in physical fatigue at the end of treatment and at one month as compared with sham stimulation. No significant effect was detected for cognitive fatigue. In terms of secondary outcomes, active transcranial direct current stimulation was associated with an improvement in depressive symptoms at the end of treatment. The treatment had no effects on quality of life. All the adverse events reported were mild and transient, with no differences between the active stimulation and sham stimulation groups. In conclusion, our results suggest that transcranial direct current stimulation on the dorsolateral prefrontal cortex may improve physical fatigue. Further studies are needed to confirm these findings and optimize stimulation protocols.

Post-COVID cognitive dysfunction: current status and research recommendations for high risk population

“… 97 Conversely, a study conducted in Spain found that eight sessions of tDCS targeting the left dorsolateral prefrontal cortex were effective for the treatment of physical fatigue but had no effect on cognition in post-COVID patients with fatigue. 98 Two studies conducted in Germany and Brazil proposed a 3-week and 4-week neuromodulation therapy course, respectively, consisting of tDCS-assisted cognitive training in PCCD, with cognitive performance as the primary outcome ( NCT04944147 , NCT05389592 ). 99 Another study in Hong Kong, China, is currently testing the effects of transcranial pulse stimulation (TPS) for young adults with depression after the COVID-19 pandemic, with cognitive function as a secondary outcome ( NCT05006365 ).…”

Cognitive profile in multiple sclerosis and post-COVID condition: a comparative study using a unified taxonomy

“…This may suggest common mechanisms and neural underpinnings in fatigue and cognitive dysfunction in both disorders, as has been recently described 9 . This opens the way to test new therapies for fatigue based on their association with functional brain changes, such as non-invasive brain stimulation, which have shown positive effects in two clinical trials 47 , 48 . However, at the same time, the lower correlation with neuropsychological tests and the greater severity of fatigue in PCC suggest the existence of other mechanisms (probably not dependent on the central nervous system and including systemic processes such as immune mechanisms, mitochondrial dysfunction or muscle abnormalities) involved in the pathophysiology of fatigue in PCC 24 , 49 , 50 .…”

Efficacy and safety of acupuncture treatment for fatigue after COVID-19 infection: study protocol for a pilot randomized sham-controlled trial

“…Furthermore, while the current clinical trials have rapidly accumulated, some treatments (e.g., transcranial direct current stimulation) have demonstrated efficacy on fatigue in post-COVID patients. Therefore, we might consider 3-arm RCT to compare the effectiveness of acupuncture, sham acupuncture and usual care ( 33 ).…”