With increasing focus being placed on the long-term impact COVID-19 can have, and the demand for effective treatments also growing concurrently, Marom Bikson (New York City, USA) outlines the potential neuromodulation holds regarding this unmet need.
There is an urgent need to best understand and develop treatments for long-COVID, or neuro-COVID, more formally called post-acute sequelae of SARS-CoV-2 infection (PASC). PASC can be defined by persisting (>1 month) symptoms following COVID-19 illness. It affects up to 20% of survivors, often with debilitating consequences and, as yet, who is suspectable to PASC and what causes it remains to be determined.
While PASC symptoms vary between individuals and can appear as a constellation of symptoms, its impairment of brain functions defines its core syndrome. Central fatigue and cognitive dysfunction, or ‘brain fog’, are the most reported symptoms, and often disable otherwise healthy individuals (i.e. preventing their return to work). Given the prevalence of PASC, and its long-lasting and debilitating nature, there is an urgent need to develop treatments—even as questions on how PASC develops are researched.
Neuromodulation includes a range of medical devices that apply energy to the body for therapeutic purposes. Most commonly, this involves application of electrical stimulation to the brain or nerves. Some neuromodulation devices are implanted, like pacemakers for the brain, while others require repeated visits to medical centres, or are battery-powered and can be used at home. Because neuromodulation devices can exert powerful therapeutic effects on the nervous systems and because, in non-COVID patients, neuromodulation treatments target many of the same symptoms reported in PASC, medical researchers are anxious to test neuromodulation for long-COVID.
Several trials of neuromodulation for COVID-19 are already running or have been completed. These have focused largely on two forms of battery-powered neuromodulation. The first applies electricity to either the neck or the ear in order to activate the vagus nerve. The vagus nerve is a branch of the nervous system connecting the brain to many peripheral organs and among the many functions it controls is anti-inflammatory responses. If COVID-19 involves an extreme and undesired anti-inflammatory response, vagus nerve stimulation (VNS) might reverse or treat COVID-related disorders.
A second form of neuromodulation being tested for PASC is a wearable cap that directs energy to the brain—referred to as transcranial direct current stimulation (tDCS). Early trials suggest tDCS may benefit individuals suffering from PASC, and NYU Langone Health in New York, USA is among the medical centres now offering tDCS services.
Low-intensity neuromodulation techniques, such as VNS and tDCS, are considered safe and well-tolerated, so much so that they are used in healthy volunteers in experiments on normal brain function. This will favourably factor into condensing the risk versus benefit of any new treatment. Ongoing and expanded studies are needed to prove if neuromodulation is effective for PASC, including understanding which type of treatment should be used for which patients.
Because COVID-19 is ubiquitous and will become endemic, PASC is especially troublesome in regard to cumulative disease burden. While vaccines and drugs are US Food and Drug Administration (FDA)-approved to moderate short-term symptoms, protection against PASC is unclear. The success of neuromodulation for PASC will depend on identifying device- and symptom-specific mechanisms. Given the unknowns about PASC itself, one method for doing this is to measure biomarkers of disease progression and response to treatment. Ultimately, home-based neuromodulation should be integrated with wearable health monitors and telemedicine, thereby supporting fully remote comprehensive treatment protocols.
Results on neuromodulation for COVID-19 were shared at the recent International Neuromodulation Society (INS) congress (21–26 May 2022, Barcelona, Spain) and more are set to be presented at the Neuroergonomics and NYC Neuromodulation Conferences (28 July–1 August 2022, New York City, USA).
Marom Bikson is the Shames Professor of Biomedical Engineering at the City College of New York in New York City, USA. Bikson’s laboratory works to translate basic research on brain function into the development of new medical devices.