Brain Stimulation in Long COVID

Cognitive problems and severe fatigue are two frequently occurring symptoms in long COVID, also known as Post-Covid Condition or Post-Acute Sequelae of COVID-19 (PASC), and their causes are currently unknown. Previous studies have shown reduced blood flow and increased inflammation in the brains of people with PASC. These brain processes are related to fatigue and cognitive problems. In other conditions, these disrupted brain processes have been treated safely and successfully with non-invasive brain stimulation. This may offer an effective treatment for people with PASC. The main goal of this clinical trial is to see whether non-invasive brain stimulation called repetitive transcranial magnetic stimulation (rTMS) can reduce fatigue in adults with PASC who also have trouble concentrating. rTMS uses short magnetic pulses on the scalp to gently stimulate a small brain area. In this study, 66 adults with PASC will be included, recruited through the Post-COVID Network Netherlands. Participants will be randomly assigned to receive either active rTMS or sham (placebo) rTMS. Sham rTMS feels and looks similar to the active treatment, but it does not generate effective magnetic pulses. The brain area that will be targeted is personalized using a brain scan (MRI) during a planning task. All participants will receive 24 rTMS sessions over six weeks (four per week). Fatigue will be measured within two weeks before and two weeks after treatment to determine whether active rTMS works better than sham. We will also look at cognition, brain connectivity and blood flow, signs of (neuro)inflammation, daily activity using an activity watch, and questionnaires about quality of life, mood, and sleep. Follow-up on cognition and questionnaires will take place 3 and 6 months after the end of the treatment.