Acupuncture for cognitive functions in post-COVID-19 condition: study protocol of a three-armed, randomized controlled trial with multimodal MRI.

Background: Post-COVID-19 condition (PCC), commonly called long COVID, is a prevalent sequela of SARS-CoV-2 infection and can affect multiple organ systems. Cognitive dysfunction is one of the most common symptoms in PCC, with a prevalence of 22%. It can persist for years and significantly reduce patients' quality of life. The brain network is the neural basis underlying human cognitive processes. Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) studies have revealed that cognitive impairments across attention, memory, executive function, and language are associated with alterations in network characteristics for PCC. Currently, there is no accepted therapy for cognitive impairment in PCC. Acupuncture has the potential to improve cognitive deficits in PCC. This trial aims to investigate the effect of acupuncture on cognitive functions in patients with PCC, and to explore the underlying mechanism of its effects on cognition in this condition using DTI and fMRI. Methods: In this three-armed, randomized controlled trial, 117 PCC patients with cognitive symptoms will be randomly assigned in a 1:1:1 ratio to verum acupuncture (VA), sham acupuncture (SA), or a waitlist control group. Participants in the VA and SA groups will receive three sessions of treatment per week for 8 weeks. The primary outcome measures are the changes in Addenbrooke's Cognitive Examination-III (ACE-III) total score and phonemic fluency test score at week 8. The secondary outcome measures include the Digit Span Test (DST), Symbol Digit Modality Test (SDMT), Trail Making Test (TMT), Rey's Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure Test (RCFT), Stroop Color Word Test (SCWT), category fluency test, action fluency test, and Boston Naming Test (BNT-30), as well as global and regional topological measures of structural and functional brain networks constructed from DTI and fMRI data. Additionally, the Fatigue Severity Scale (FSS), the Generalized Anxiety Disorder-7 (GAD-7), the 24-item Hamilton Depression Scale (HAMD-24), and the MOS 36-item Short Form Health Survey (SF-36) will also be measured. Discussion: The results of this study will reveal the effect of acupuncture treatment on cognitive functions for PCC and provide insights into the mechanisms by which acupuncture may improve cognition in PCC. Clinical trial registration: ClinicalTrials.gov (www.clinicaltrials.gov), identifier: NCT07355751.