Targeting Cognitive Impairment of Long COVID With Brain Stimulation

Leigh Charvet, PhD

In recent studies, the most common symptoms reported of long COVID from patients is cognitive dysfunction, known to impair the quality of life in adults significantly. Mostly described as "brain fog," this cognitive symptom burden can cause patients to have trouble remembering things or problems with focusing on tasks. These cognitive problems are also associated with anxiety and depression.¹

Gathering a comprehensive understanding into the long-term effects, mechanisms, and therapies of long COVID will depend on concerted efforts from researchers and patients.² Recently, investigators initiated enrollment into the randomized RECOVER-NEURO (NCT05965752) trial, a study assessing cognitive dysfunction associated with long COVID. 3 In total, the trial plans to have 315 patients with long COVID for a 10-week study intervention period, with a follow-up visit after 90 days.

Coprincipal investigator Leigh Charvet, PhD, professor of neurology, NYU Grossman School of Medicine, recently sat down in an interview with NeurologyLive® to discuss why remote engagement of patients in clinical trials, like RECOVER-NEURO, is important, especially for conditions like long COVID. She talked about the length of the trial, and the timeline for obtaining results. In addition, Charvet spoke about the innovative approaches that are being used in the trial, and how they might contribute to addressing long COVID symptoms.

NeurologyLive: Could you provide an overview of the research you're planning to conduct?

Leigh Charvet, PhD: As part of the RECOVER Initiative, there's treatment arms that are targeting symptoms of long COVID in a trial called RECOVER-NEURO. The treatment in the trial is targeting specifically the symptom cluster that's led by cognitive impairment, often referred to as brain fog. This trial will aim to target cognitive dysfunction in the context of long COVID. There are 5 treatment arms where participants across the country will be evaluated and enrolled at their local sites. It will be remote and home-based, which is a unique and exciting feature of this trial.

Our lab has a lot of experience with home-based delivery of treatments, which we call remotely supervised through video connection or video visits. All the participants and the sites will be receiving the intervention, according to the arms of the study. We'll ship them a study kit, and be with them for 50 sessions total, with daily sessions of treatment. The treatment will either be cognitive training with an online cognitive remediation program called BrainHQ, which we have a lot of experience working, or a comparator. Some patients will receive BrainHQ with transcranial Direct Current Stimulation (tDCS), which is something that our lab has really worked for many years to develop and evaluate. The idea is that the stimulation can be paired with the cognitive training to boost that outcome. The other arm is the comparator paired with the active tDCS, which is called sham tDCS, or placebo. Then, the fifth arm will have the BrainHQ. We'll also work with the Mount Sinai group to receive individualized or group based cognitive remediation through a program they’ve developed called Past Core

There's a lot going on. I think we're really excited because of our long background in telerehabilitation and reaching people in their homes in a rigorous way for trials. We'll be centrally distributing these interventions across the country and monitoring in that way.

Do you believe that engaging patients in remote clinical trials is important?

It's very important. I've been in the telehabilitation space for clinical trials for almost 12 years now. Right before COVID, we used to have to make a really strong case for why we needed to reach people in their homes, even before treatments had been fully established to be studied. Anything that requires daily visit to clinic or treatments that are most effective and repeated days span either weeks or even months. Sometimes it's just not reasonable at all to ask anybody to come to clinic every day, no matter where you're located. We're in midtown Manhattan and we did a survey of our patients on the cost in terms of dollars and of time that they spent to come in. We're all 5-10 miles away from each other but for them to travel to our clinic for one single visit—if you add that up for the 50 sessions in this trial, it's staggering. I really believe that we have moved the dial along as a result of what we went through with COVID. The home-based remote supervision is really a way to deliver a lot of these treatments to people.

We need to know exactly what's being delivered in the head of the monitoring. We've spent a lot of time and effort to develop standards so that what we're replicating exactly what we do here in the lab to the home setting. We have lots of stops and checks and criteria along the way, ensuring safety, as well as the rigor and reproducibility of the research.

How long are you going through with the trial?

It's a long period of intervention. It's 10 weeks for each participant, but we're hoping to rapidly complete the trials. Our goal is very ambitious because we want answers to everything and the whole world wants answers about treatments that we can use to help people. So definitely in 2 years or even before then. We want to try to actively and efficiently get everything up and running to get answers as soon as possible.

We have so many people living with unmet needs that we just don't have adequate treatment for right now. We have treatments that are not effective or treatments that are maybe effective but can't be widely disseminated or accessible. We still need to stick with evidence-based guidance and that's what we're really trying to do in the most efficient way possible, to meet the needs of so many people living with the symptom burden.

What are you excited about and looking forward to with this research?

I'm excited to start evaluating treatments to help so many people that are living with this symptom burden. I think it's particularly exciting and innovative that we're doing it with interventions being delivered remotely. I think it’s definitely necessary, but innovation is there as well in terms of technology reaching people in their homes. Also, the unique innovation of including noninvasive brain stimulation with the tDCS is very cutting edge, incorporating the best data that we have in a rapid evaluation as a potential treatment.

Transcript edited for clarity.

REFERENCES
1. Hugon J, Msika EF, Queneau M, Farid K, Paquet C. Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex. J Neurol. 2022;269(1):44-46. doi:10.1007/s00415-021-10655-x
2. Gonzalez-Fernandez E, Huang J. Cognitive Aspects of COVID-19. Curr Neurol Neurosci Rep. 2023;23(9):531-538. doi:10.1007/s11910-023-01286-y
3. RECOVER-NEURO enrolls first participant in trial. News Release. RECOVER. Published September 5, 2023. Accessed September 11, 2023. https://recovercovid.org/updates/recover-neuro-enrolls-first-participant