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.