An estimated 6 percent of adults in the United States are currently experiencing post-acute sequelae of COVID-19 (PASC), also known as “long COVID.” To treat the syndrome’s neurologic symptoms, some researchers are investigating transcranial direct current stimulation (tDCS), an experimental therapy that has been used successfully to mitigate cognitive, motor, speech, and mood problems that can occur in a wide range of neurologic and psychiatric conditions. To date, however, only a few small clinical trials of tDCS in patients with PASC have been completed.

The NIH recently launched a larger study that aims, in part, to clarify the method’s utility. The RECOVER-NEURO trial is testing tDCS alongside other interventions for cognitive dysfunction related to long COVID, including brain fog, memory deficits, and difficulties with attention and problem-solving.

“This is the first nationwide, controlled clinical trial to directly address PASC-mediated cognitive dysfunction.”

Leigh E. Charvet, PhD

The phase 2 clinical trial will evaluate a web-based brain training program, BrainHQ, both alone and in tandem with tDCS or PASC-Cognitive Recovery, a web-based goal-management training program for people with PASC. BrainHQ will also be tested against an active comparator (video games) and paired with sham tDCS using devices from the manufacturer.

These therapies will be administered via telehealth to patients across the United States under the supervision of co-principal investigator Leigh E. Charvet, PhD, director of the tDCS Program at NYU Langone Health and a leading researcher of tDCS’s potential for treating PASC. “This is the first nationwide, controlled clinical trial to directly address PASC-mediated cognitive dysfunction,” Dr. Charvet notes.

Applying Findings from Multiple Sclerosis

Over the past decade, Dr. Charvet has pioneered the use of home-based cognitive rehabilitation for patients with multiple sclerosis (MS). She was an early adopter of BrainHQ, whose efficacy she helped establish through clinical trials. Adding tDCS to that regimen, she found, significantly enhanced its cognitive impacts—a discovery that led her to shift her research focus to expanding the use of tDCS to reach patients at home through telehealth.

The method has shown promise for patients with MS, stroke, Parkinson’s disease, and many other conditions, improving cognitive and motor symptoms, for instance, and also as a treatment for depression. “Imaging studies show that functional targeting with tDCS can strengthen neuroplasticity and increase blood flow in the brain,” she explains. “This can translate to a wide range of clinical benefits.”

In 2019, Dr. Charvet began offering tDCS via telehealth to patients across the United States. The following year, when the COVID-19 pandemic struck, people with PASC started calling the clinic, asking if they could try tDCS. “They were just desperate for treatment,” Dr. Charvet recalls. She and her team worked with patients with PASC and their referring physicians to design remote treatment protocols, sparing COVID long-haulers—who were often experiencing severe debilitation—the necessity of office visits.

“Our goal is to provide patients with long COVID an accessible, evidence-based treatment approach that will improve their quality of life.”

Anecdotally, the initial results were promising. “Our patients told us they were getting better,” Dr. Charvet says. Since then, she and her team have expanded both the clinical tDCS Program and their research efforts.

Dr. Charvet has collaborated with colleagues at NYU Langone and elsewhere on preliminary studies of tDCS for PASC, which suggest that the method, paired with rehabilitation programs, can reduce fatigue and anxiety and improve cognitive functions in people with the syndrome. She also helped design the protocol for the RECOVER-NEURO trial—part of the NIH’s RECOVER initiative, which strives to understand the biological processes driving long COVID and to identify effective treatments. Colleague Stuart D. Katz, MD, director of NYU Langone’s heart failure program, is principal investigator of the RECOVER Clinical Science Core.

Seeking Answers with a Nationwide Trial

RECOVER-NEURO will enroll a target of 315 patients from centers across the United States to its five arms, Dr. Charvet says. Once enrolled, participants will be referred to NYU Langone, which will centrally deliver the interventions to patients at home using their established telehealth protocols. Each participant will have five, 30-minute telehealth sessions per week for 10 weeks. The trial’s primary objective is to evaluate each intervention’s effect on cognitive function versus a comparator.

“Our goal,” says Dr. Charvet, “is to be able to provide patients with long COVID an accessible, evidence-based treatment approach that will improve their quality of life and enable them to return to their responsibilities at home and at work.”