A randomized comparative feasibility study of neuromodulation and cognitive training for post-COVID fatigue, 2025, Oliver-Mas et al.

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A randomized comparative feasibility study of neuromodulation and cognitive training for post-COVID fatigue
Oliver-Mas, Silvia; Matias-Guiu, Jordi A.; Delgado-Alonso, Cristina; Gil-Martínez, Lidia; Cuevas, Constanza; Polidura, Carmen; Fernández-Romero, Lucía; Matias-Guiu, Andreu; Gómez-Ruiz, Natividad; Gil-Moreno, María José; Yus-Fuertes, Miguel; Matias-Guiu, Jorge; Diez-Cirarda, Maria

Fatigue and cognitive deficits are common and disabling symptoms in patients experiencing post-COVID condition. This randomized parallel study aimed to evaluate the effects of transcranial direct current stimulation (tDCS) over the primary motor cortex combined with cognitive training (M1 + CT), compared to tDCS over the dorsolateral prefrontal cortex with cognitive training (DLPFC + CT), on fatigue, cognition, and other clinical symptoms in post-COVID.

Sixty-three patients completed the treatment (n = 32 in the M1 + CT group and n = 31 in the DLPFC + CT group) with a mean age of 47 years and an average symptom duration of 32 months. Both groups underwent comprehensive neuropsychological and clinical evaluations, including ecological momentary assessments of fatigue, at baseline, post-treatment, and one-month follow-up. The Fatigue Severity Scale (FSS) was used as the primary endpoint. Patients were randomly assigned to the M1 + CT or DLPFC + CT groups and received 15 sessions of tDCS administered concurrently with adaptive CT.

The M1 + CT group showed a slightly higher efficacy in reducing fatigue and improving sleep quality than the DLPFC + CT group. Both groups demonstrated significant improvements in cognition, anxiety, depression, pain, and sleep quality. These improvements were sustained over time.

These findings indicate that tDCS combined with cognitive training is a feasible, safe, and effective approach for reducing fatigue and enhancing cognition in post-COVID patients. The results highlight the potential of brain stimulation and cognitive training to alleviate fatigue and cognitive impairment in post-COVID, warranting further confirmation through additional randomized controlled trials.

TRIAL REGISTRATION
ClinicalTrials.gov NCT05753202.

Web | PDF | Nature Scientific Reports | Open Access
 
These findings indicate that tDCS combined with cognitive training is a feasible, safe, and effective approach for reducing fatigue and enhancing cognition in post-COVID patients.
No, it does not prove effectiveness, the study isn’t designed for it.

Furthermore, the intra-group change in FSS, the primary endpoint, is below the MCID.
The primary endpoint of the present study was fatigue, assessed using the Fatigue Severity Scale (FSS). Previous studies have identified a 0.88-point change in the FSS as clinically significant57
They cite a study on MS that found an MCID of 0.88 on the 1-7 score, which is 14.7 % of the scale (9 items rated 1-7, so 54 steps), equating to 7.9 points.

For RA, the MCID for FSS is 20 % of the scale, or 10.8 points, so they’ve chosen an MCID at the lower end of the range.

They found a change in FSS of ~6 points, well below the MCID.
Physical fatigue measured through the FSS showed a significant main effect of time (pbonf < 0.001), and no significant time-per-group interaction was found. Post hoc comparisons revealed a significant time effect between baseline and post-treatment (mean difference of 5.984, pbonf < 0.001) and between baseline and follow-up (mean difference of 6.016, pbonf < 0.001), but not between post-treatment and follow-up.
They then go on to talk about some kind of «ecological» measurement of fatigue with a 1-10 Likert scale the participants answered every day during the treatment. They got a small change here, but I can’t say it’s very impressive considering the open-label nature of the trial.
IMG_0265.webp

Also, there’s no mention of this measurement in the trial registration.

Nature, this is a bad paper that you should not have published.
 
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