Non-Invasive Brain Stimulation for Post-COVID-19 Conditions: A Systematic Review

Alongside the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the number of patients with persistent symptoms following acute infection with SARS-CoV-2 is of concern. It is estimated that at least 65 million people worldwide meet criteria for what the World Health Organization (WHO) defines as "post-COVID-19 condition" - a multisystem disease comprising a wide range of symptoms. Effective treatments are lacking. In the present review, we aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post-COVID-19.

After pre-registration with PROSPERO, the review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). The four electronic databases PubMed/MEDLINE, PsycINFO, Web of Science and Scopus were systematically searched for all relevant studies through April 2nd, 2024. Two independent investigators selected empirical papers that reported on the application of non- or minimally invasive brain stimulation in patients with post-COVID-19 conditions.

A total of 19 studies were identified, one using transcutaneous vagus nerve stimulation (tVNS), another using transorbital alternating current stimulation (toACS), 6 studies on transcranial magnetic stimulation (TMS) and 11 studies on transcranial direct current stimulation (tDCS) for the treatment of post-COVID-19 symptoms.

Existing studies report first promising results, illustrating improvement in clinical outcome parameters. Yet, the mechanistic understanding of post-COVID-19 and how brain stimulation techniques may be benefitial are limited. Directions for future research in the field are discussed.