Transcranial direct current stimulation combined with aerobic exercise for motor, mood and cognitive symptoms in long COVID: a randomized, sham-controlled feasibility trial

 INTRODUCTION: The COVID-19 pandemic left millions of people with persistent disorders. Among these, long COVID is frequently associated with motor, mood, and cognitive impairments, significantly reducing quality of life.

Objectives

To evaluate the feasibility of a randomized, sham-controlled trial of a two-week protocol combining transcranial direct current stimulation (tDCS) and aerobic exercise in individuals with long COVID, against pre-specified criteria for recruitment, retention, adherence, assessment burden, acceptability and safety. Motor, mood and cognitive outcomes were exploratory.

Methods

AND MATERIALS: Participants were randomized (1:1) to real (2 mA, 30 min, left M1) or sham tDCS, both combined with treadmill exercise (64–76% max heart rate). Randomization used a computer-generated sequence, with allocation concealed in sealed opaque envelopes; participants and outcome assessors were blinded. The protocol comprised 13 sessions: baseline, 10 interventions, and two follow-ups. Feasibility was assessed through resources, management, and safety; clinical outcomes included motor, mood, and cognitive functions.

Results

Of 76 individuals contacted, 44 were assessed for eligibility and 10 were randomized (5 per group). All participants completed the intervention and post-intervention reassessment, and 8 completed the follow-up (80% retention). Adherence was high, and assessments remained under 120 minutes. All participants reported perceived benefits after the intervention (90% at follow-up); no serious adverse events occurred, and mild adverse effects were reported by all participants in both groups (most commonly drowsiness, tingling and fatigue), with no between-group differences. Fatigue decreased in both groups, with no significant between-group differences in any clinical outcome.

Conclusion

A randomized, sham-controlled trial of tDCS combined with aerobic exercise in long COVID is feasible, and the protocol was safe and acceptable. The pre-specified feasibility criteria were met, supporting progression to an adequately powered trial with adjustments to recruitment strategies and delivery format.